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8793674
Valve replacement for aortic stenosis with severe congestive heart failure and pulmonary hypertension.
Significant pulmonary hypertension in aortic stenosis is evidence of severe dysfunction of the left ventricle. It is also a predictor of a bad prognosis in the natural course of the disease. This study was performed to evaluate the changes in the hemodynamic parameters of pulmonary circulation at rest and effort in patients who had significant pulmonary hypertension preoperatively and underwent valve replacement.
8793673
The potential for normal long term survival and morbidity rates after valve replacement for aortic stenosis.
The sequelae of early aortic valve replacement (AVR) for aortic stenosis (AS) are controversial, with an increasing body of opinion regarding the patient risk profile as having an influence on long term survival and prosthesis-related morbidity rates. We therefore undertook parison of the morbidity and mortality rates of the patients undergoing AVR at our institution over a 22 year period with those in the background population to establish whether early intervention leads to an increased incidence of either.
8793675
Aortic valve replacement: better myocardial protection by cold or warm retrograde blood cardioplegia?
To determine whether warm blood cardioplegia (BCP) is superior to cold BCP in terms of myocardial protection, pared warm (37 degrees C) and cold (4 degrees C) continuous retrograde administration of BCP in 40 patients undergoing aortic valve replacement (AVR) in a prospective, randomized study.
8793676
Repair of aortic cusp traumatic laceration caused by cardiac catheterization.
A case of iatrogenic aortic insufficiency due to laceration of the aortic right coronary leaflet at the time of diagnostic heart catheterization is presented. The situation was remedied by repairing the lacerated leaflet.
8793677
Peculiar patterns of aortic regurgitation and carotid pulse due to dysfunction of a Medtronic Hall prosthetic valve: a case report.
We describe a patient with dysfunction of a Medtronic Hall prosthetic valve showing peculiar patterns of aortic regurgitation and carotid pulse caused by valvular thrombosis. The aortic regurgitation was considered to be caused by a significant delay in prosthetic valve closure, manifested by a peculiar regurgitation pattern limited to early diastole, in association with widely split closing clicks and an abnormally low dicrotic notch in the carotid pulse. At surgery, fibrin thrombi were noted just below the prosthetic ring in the minor outflow region which restricted disc movement. The fibrin thrombi were removed and the valve was rotated 90 degrees. Following reoperation, all abnormalities disappeared.
8793679
Surgery for rheumatic mitral regurgitation in patients below twenty years of age. An analysis of failures.
Mitral valve repair is less stable in rheumatic than in degenerative disease. This failure rate is inversely related to the age of the patient. Based on our clinical experience, we selected the group of patients with the worst results for this study: (i) rheumatic, (ii) age 20 or under, (iii) pure mitral regurgitation (MR), and, (iv) no aortic disease.
8793680
Long term results of mitral valve replacement with preservation of the posterior leaflet.
It monly held that preservation of the annulo-ventricular continuity during mitral valve replacement has a beneficial effect on postoperative ventricular function. This paper presents our eight-year experience with this technique.
8793681
Balloon mitral commissurotomy in a patient with situs inversus and dextrocardia.
A patient with situs inversus and dextrocardia in whom a successful balloon missurotomy for symptomatic rheumatic mitral stenosis was performed after appropriate modifications in the technique of transseptal catheterization is described.
8793682
"Diverticula" of anterior mitral valve leaflet as a cause of subvalvular aortic stenosis.
A 77-year-old male patient presented with symptoms of shortness of breath, fatigue, chest pain on exertion and dizziness. Transthoracic echocardiography suggested the presence of a diaphragmatic type of obstruction in the subaortic area of the left ventricular outflow tract. The systolic peak gradient at rest was 34 mmHg with a mean of 23 mmHg. Cardiac catheterization demonstrated rounded radiolucencies in the left ventricular outflow tract in the form of two "pouches" that moved back and forth causing subaortic stenosis. There was also a 70% stenosis of the left anterior descending coronary artery. Left ventricular function was normal. At surgery, a transesophageal echocardiogram demonstrated two distinct pouches arising from the anterior leaflet of the mitral valve. The larger of the two originated near the free edge of the leaflet and was attached via a chord to the membranous septum traversing the subaortic area of the left ventricular outflow tract. The patient underwent a left internal mammary to left anterior descending bypass graft, excision of the larger pouch and over-sewing of the smaller pouch. The excision and repair were performed through the aortic root and aortic valve. The patient made an plicated recovery and on follow up his symptoms disappeared. This case shows the excellent results that can be obtained by surgery of diverticula of the mitral valve causing intermittent subaortic stenosis, a rare pathologic entity, morphologically different from the classical diaphragmatic subaortic stenosis.
8793683
Double valve replacement with the Carpentier-Edwards pericardial valve: 10-year results.
The first generation of pericardial valves was withdrawn from the market because of an excessive rate of premature failure. With an original design, the Carpentier-Edwards pericardial valve promised improved results.
8793684
Feasibility evaluation of a new pericardial bioprosthesis with dye mediated photo-oxidized bovine pericardial tissue.
In an attempt to e the problem of calcification of bioprostheses, a novel bovine pericardial tissue valve preserved with a non-aldehyde, dye mediated photo-oxidation process (PhotoFixTM) developed by CarboMedics, Inc. The device was evaluated by implantation in the mitral position of juvenile sheep with a mean age of 3.5 months.
8793685
Low-profile porcine bioprosthesis (Liotta): pathologic findings and mode of failure in the long-term.
The Liotta low profile porcine bioprosthesis (LBP) was designed in order to plications due to excessive protrusion of the stent prongs in the left ventricle.
8793686
A hemodynamic comparison of Omniscience and Medtronic Hall aortic prostheses.
Preliminary reports have suggested hemodynamic disparities between single leaflet tilting disc prostheses. We tested the hypothesis that similarities in prosthetic design may not necessarily indicate hemodynamic equivalence.
8793687
Mechanical valve replacement in congenital heart disease.
Mechanical valves are the prosthesis of choice in valve replacement in children. However, the problem of somatic growth leading to patient-valve mismatch remains present, and the appropriate anticoagulation regimen remains controversial. We present our experience of valve replacement in a young population over 20 years.
8793688
Formaldehyde replaces glutaraldehyde in porcine bioprosthetic heart valves.
In the production of porcine bioprostheses, the initial glutaraldehyde treatment is often followed by a short incubation in formaldehyde to ensure sterility of the valve. It is assumed that the glutaraldehyde cross links are stable and that the formaldehyde step does not alter the glutaraldehyde incorporated. The objective of this study was to determine whether the formaldehyde interacts with the tissue to cause changes in the position.
8793689
Guidelines for antihypertensive therapy: problems with a strategy based on absolute cardiovascular risk.
It has been suggested that selection for antihypertensive therapy should be based on absolute risk of a cardiovascular disease (CVD) event and that treatment should be offered only if the 10-year risk exceeds 20%. Although interesting and challenging, this strategy would have the effect of greatly emphasizing treatment of the elderly and downplaying treatment of the middle-aged. It is argued in this paper that the use of one and the same time-frame for all age groups is illogical; some inverse age-related adjustment is needed. In addition, it is suggested that selection for active treatment would be better based not on the total absolute risk of CVD but rather on the marginal hypertensive risk (i.e. that part of the total risk which can be attributed to raised blood pressure). Problems in the use of antihypertensive drugs in people with 'high normal' blood pressure in order pensate for risk factors such as obesity, hyperlipidaemia and smoking are discussed. The effect of antihypertensive treatment administered in large-scale trials to the most hypertensive control subjects has been (and continues to be) largely ignored; it should be taken into account in all calculations in this field. A policy based on absolute risk is certainly worth examining but it should not be considered self-evidently correct and needs testing in all its aspects before it is adopted on a large scale.
8793691
Controversies surrounding erythrocyte sodium-lithium countertransport.
Interest originally arose in ouabain-insensitive lithium transport across erythrocyte membranes when it was found that lithium could substitute for sodium, either undergoing 1:1 lithium exchange or 1:1 sodium-lithium countertransport in a manner that follows Michaelis-Menten kinetics. Elevation of the sodium-lithium countertransport activity in hypertension was first noted in 1980 and found to be a genetically linked phenomenon. This observation has since been confirmed on several occasions and associations with other diseases such as diabetes have been noted. Nevertheless, many unanswered questions remain about the clinical significance of disturbed sodium-lithium countertransport and its pathological basis.
8793692
Effect of ageing and hypertension on endothelial modulation of ouabain-induced contraction and sodium pump activity in the rat aorta.
To investigate the endothelial modulation of the rat thoracic aorta sodium-potassium ATPase activity and its possible alteration by ageing and hypertension.
8793693
Feelings of exhaustion, emotional distress, and pituitary and adrenocortical hormones in borderline hypertension.
To examine whether feelings of exhaustion and emotional distress reflecting chronic perceived stress contribute to a pattern of pituitary and adrenocortical responses that would in turn be able to distinguish borderline hypertensives from normotensive controls.
8793694
Development of enzyme-linked immunoassays for human angiotensin I converting enzyme suitable for large-scale studies.
To develop and validate a simple immunological assay for human angiotensin converting enzyme (ACE) based on monoclonal antibodies.
8793695
Lack of influence of menopause on blood pressure and cardiovascular risk profile: a 16-year longitudinal study concerning a cohort of 568 women.
To analyse the effect of menopause on blood pressure and cardiovascular risk.
8793696
Dietary electrolyte intake and blood pressure in older subjects: the Rotterdam Study.
To examine the relation between dietary electrolyte intake and blood pressure in older people.
8793697
Prognostic value of a history of hypertension in 11,483 patients with acute myocardial infarction treated with thrombolysis. GISSI-2 Investigators. Gruppo Italiano per lo Studio della, Sopravvivena nell'Infarto Miocardico.
To assess the prognostic value of a history of hypertension in patients with acute myocardial infarction (AMI) treated with thrombolysis.
8793698
Altered contractile function in isoproterenol-induced hypertrophied rat heart.
To study the calcium-dependent mechanisms contributing to altered contractile function in isoproterenol-induced ventricular hypertrophy of the rat heart.
8793699
Similarities and differences in structural and functional changes of left ventricle and carotid arteries in young borderline hypertensives and in athletes.
To investigate the association between increased left ventricular mass and the intima-media thickening of carotid arteries in hypertensive patients and the simultaneous involvement of the heart and the conductance vessels by the hypertensive process.
8793700
Prostaglandins and renal function in hypertensive patients with unilateral renal artery stenosis and patients with essential hypertension.
This study was designed pare the effects of prostaglandin synthesis inhibition on calculated preglomerular and postglomerular resistance in hypertensive patients with unilateral renal artery stenosis (RAS) and in patients with essential hypertension.
8793701
Non-pharmacological management of hypertension: results from interviews with 100 general practitioners.
To describe the type and level of non-pharmacological management offered by general practitioners for essential hypertension.
8793702
Exercise and weight control in sedentary overweight men: effects on clinic and ambulatory blood pressure.
To examine whether restriction of caloric intake and exercise of vigorous intensity can independently and additively influence clinic and ambulatory blood pressures in sedentary overweight men.
8793703
Difference between office and ambulatory blood pressure and response to antihypertensive treatment.
To investigate whether a clinic-ambulatory blood pressure difference persists with time under active drug treatment or placebo and to determine whether and how it interferes with the evaluation of the efficacy of antihypertensive treatment.
8793704
Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension.
To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients.
8793706
Incidence and risk factors for pneumonia in HIV infected and non-infected drug users.
To study the incidence and risk factors for pneumonia in a cohort of HIV infected and non-infected drug users (DU).
8793708
An economic evaluation of universal vaccination against hepatitis B virus.
This report presents the results of an economic evaluation utilizing U.K. data, into a vaccination programme against Hepatitis B using a genetically engineered, yeast-derived vaccine, Engerix B. Cost-effectiveness ratios were calculated for four different programmes: an infant vaccination programme; a child vaccination programme; an adolescent vaccination programme; and bined child and adolescent programme. For each programme, the number of annual cohorts vaccinated was varied from 1 to 25. The e was defined as incremental life years gained, and the results are reported as costs per incremental life-year gained. Benefits were calculated in both undiscounted and discounted forms. All costs were discounted. The discount rate used was 6%. All major epidemiological and cost assumptions were subjected to a sensitivity analysis. Baseline results with benefits discounted range from pounds188015 to pounds301365 per life year gained, depending on the duration of programme and vaccination strategy. With benefits undiscounted, parable range is from pounds5234 to pounds13034.
8793707
In vitro induction of nitric oxide by an extract of Plasmodium falciparum.
Malarial illness and pathology is generally accepted to be caused by material released when the infected red cells burst at schizogony. The released material has been partially purified and shown to stimulate macrophages to make TNF. We have extended this work to show that these same preparations, isolated from parasitized erythrocytes, induce the mouse macrophage cell line RAW 264.7 to produce inducible nitric oxide synthase and release nitric oxide. By using cytokine-specific antisera we have found that this induction is independent of TNF and IL-1 alpha and partly independent of IL-1 beta.
8793709
Detection of polyomaviral DNA in clinical samples from immunocompromised patients: correlation with clinical disease.
Clinical samples from promised patients were screened for polyomaviral sequences by nested polymerase chain reaction (PCR) to evaluate the association of these viral infections with progressive multifocal leukoencephalopathy (PML). JC virus (JCV) DNA was detected in 19 of 23 CSF samples and all four brain samples from patients with PML. Neither BK virus (BKV) nor simian virus 40 (SV40) DNA were detected in these samples. No evidence was found to support the hypothesis that polyomaviral DNA is present in the central nervous system of immunosuppressed patients without PML (CSF n = 67, brain n = 19). JCV DNA was not detected in any peripheral blood sample included in this study. JCV DNA was detected in urine from three of eight patients with PML, but was also amplified from three of 29 urine samples from patients without PML, JCV, and not SV40 or BKV, was associated with PML in this study.
8793710
Immunomagnetic separation and PCR detection show Shigellae to be common faecal agents in children from urban marginal communities of Costa Rica.
Culture and immunomagnetic separation-polymerase chain reaction assays (IMS-PCR) were used to isolate and identify Shigella flexneri, S. dysenteriae type I and S. sonnei in faeces from 250 children up to 5 years and from their mothers (n = 143) selected at random from a large urban munity of Costa Rica. Children hospitalized because of severe diarrhoea (n = 110) were also studied. Only S. flexneri, mainly serotype 2a, and S. sonnei were found by culture. All specimens in which Shigella was cultured were also positive by the corresponding IMS-PCR. S. flexneri was isolated by culture from 1 (0.7%) mother and 4 munity children. S. sonnei was found in 2 (0.8%) children. An additional 12 S. flexneri and four S. sonnei in munity children were found by IMS-PCR. In total, Shigella was cultured from 0.7% of mothers and 2.4% of children. By the IMS-PCR 2% of mothers and 8% of children were positive. S. flexneri was isolated by culture from 14 (12.7%) hospitalized children and S. sonnei from 1 (0.9%). An additional 11 S. flexneri and three S. sonnei were found by IMS-PCR. In total, Shigella was cultured from 13.6% of hospitalized children. By the IMS-PCR 26% of them were Shigella positive. Thus IMS-PCR was more than twice as effective in diagnosing shigellae as culture. Twelve (60%) Shigella munity children were above 3-years-old and 25% of them were under one year. Seven (35%) of the Shigella positive children had dysenteric and 9 (45%) normal stools. Half of the Shigella munity children had been weaned before the 3 months of age. By the age of 5 months, 90% of them were already weaned. Seventeen (59%) of the hospitalized Shigella positive children were under 1 year of age. The stools were watery or semiliquid in 13 (45%) and dysenteric in 12 (41%) of them. We conclude that shigellosis mon in Costa Rica and represents an important cause of severe infant diarrhoea requiring hospitalization.
8793711
Helicobacter pylori isolated from stomach corpus and antrum: comparison of DNA patterns.
The genomic DNA of Helicobacter pylori was studied in strains isolated from two different sites of the stomach: the corpus and the antrum. 70 strains of H. pylori were found in 36 patients; 34 out of the 36 patients harboured the strain in both districts analysed. Restriction endonuclease analysis with Hae III and Hind III was used pare the DNA patterns of strains isolated from the anatomical sites studied. Two pairs of DNA samples were not digested by these enzymes. 27 of the 32 pairs of the digested DNA appeared similar to each other. The analysis of chromosomal DNA in the remaining five pairs showed different electrophoretic patterns. These results indicate that the gastric mucosa can be colonized, at the same time, by strains of H. pylori with different genomic patterns, and this aspect can be important for epidemiological studies.
8793712
The organisms reported to cause infective myocarditis and pericarditis in England and Wales.
It is difficult to acquire an overall perspective of the range of organisms responsible for infective myocarditis or pericarditis, and their relative importance, as most studies have involved only case reports or case series of a single organism. This study analyses reports to the Communicable Disease Surveillance Centre, of the Public Health Laboratory Service. Reports where myocarditis or pericarditis was included as the main clinical features between 1990 and 1993 were studied. Between 1990 and 1993, 368 cases of myocarditis and/or pericarditis were reported to CDSC. Viruses were reported to cause 253 (69%) cases, bacteria were responsible for 49 (13%) cases, mycoplasma for 32 (9%) cases, chlamydia for 16 (4%) cases and Mycobacterium tuberculosis for nine (2%) cases. Infection with coxsackie B virus was most frequently associated with a mixed picture of myo/pericarditis, whereas influenzae virus was associated with pericarditis or myocarditis alone. This information will provide clinicians with details of the more likely pathogens responsible for these conditions.
8793713
Adult primary IgA nephropathy and common viral infections.
Serum samples obtained from 69 histopathologically proven IgA nephropathy (IgAN) patients and 563 healthy controls were examined to evaluate the association between IgAN mon viral infections. Antibody titres to cytomegalovirus (CMV), herpes simplex virus (HSV), Vericella-Zoster virus (VZV), Influenza A (Inf. A) and Influenza B (Inf. B) viruses were determined, using plement fixation test. The viral antibody titres were considered to be positive with dilutions of 1:8 or greater except for Epstein-Barr virus (EBV), studied using immunofluorescence, which was considered to be positive with dilutions of 1:10 or greater. The positive rate of Inf. B antibody in IgAN patients was significantly lower than that in controls. The frequency of positive CMV antibody titres was higher than for controls, but with only borderline statistical significance (P = 0.059). The frequency of positive CMV and Inf. B titres pared by age in IgAN patients and controls. but showed no statistically significant difference. Comparisons of percentage distributions at each antibody dilution level to mon virus of IgAN patients and controls, but showed no statistically significant difference. Comparisons of percentage distributions at each antibody dilution level to mon virus of IgAN patients and controls were made; however, none showed a statistically significant difference. In conclusion, no absolutely higher frequency of positive antibody titres mon viruses was demonstrated in IgAN patients in this study.
8793715
Tick bite fever in black South Africans--a rare disease?
Tick bite fever (Rickettsia conorii) is a disease which monly in South Africa. Clinical illness in the black African patient is however rare, despite high seroprevalence rates of antibodies against R. conorii reported from other areas of Southern Africa. We present two case reports of clinically apparent tick bite fever occurring in black South Africans, the first to be documented in sub-Saharan Africa, and examine possible explanations for the marked discrepancy between clinical illness and seroprevalence rates.
8793714
Toxocara titres in maternal and cord blood.
Fifty-two pairs of maternal and cord blood samples were examined for evidence of Toxocara canis antibodies. All the mothers in the study delivered normal babies at term. Seventeen (33%) of the mothers had Toxocara antibody titres of 1:50 or greater. No IgM isotype anti-Toxocara antibody was detected in the cord blood samples, evidence that transplacental toxocaral infection had not occurred. In the toxocara antibody-positive group it was found that six of 17 mothers (35%) had previously pared with three of 35 (8.6%) of the toxocara-negative mothers (P = 0.044).
8793716
Disseminated herpes simplex virus infection presenting as fever in the newborn--a lethal outcome.
The clinical course of a neonate who presented with fever and tachypnea on day 6 of life is described. He developed disseminated intravascular coagulopathy, hepatic a and expired at 14 days of age. The post mortem viral cultures from liver, adrenal and lungs were positive for HSV type 2. The fatal e of this case of fever, due to HSV infection, emphasizes the need for early treatment of suspicious cases of HSV infection. HSV should be considered in the differential diagnosis of the newborn with persistent fever unresponsive to antibiotics.
8793717
Changing pattern of Candida species in a bone marrow transplant patient.
A report on a patient with multiple myeloma, undergoing bone marrow transplant, who developed systemic fungal infection due to Candida krusei after bone marrow transplantation. The subsequent appearance of Ketoconazole resistant C. krusei is probably the first report of its kind from India. The significance of the findings is discussed.
8793718
Recurring episodes of meningitis (Mollaret's meningitis) with one showing an association with herpes simplex virus type 2.
Benign recurrent aseptic (Mollaret's) meningitis is a rare disease of unknown aetiology. We report the case of a 27-year-old woman who experienced three episodes of lymphocytic meningitis. Human Simplex Virus (HSV) type 2 DNA was detected in the CSF by PCR amplification indicating the diagnosis of recurrent HSV type 2 meningitis. Our observation suggests that search of herpes virus DNA by PCR amplification on CSF may be useful in unexplained recurrent meningitis.
8793721
Differences in capillary supply between human oro-facial, masticatory and limb muscles.
In this report we show that immunostaining of the capillary basement membrane with an antibody directed against laminin is a useful alternative in detecting the capillaries in human muscle. Using this method, the capillary supply of three embryologically, morphologically and functionally different muscle groups, oro-facial, masticatory and limb muscles, were analysed. Significant differences in capillarization between muscles and muscle groups were found. The oro-facial and masseter muscles showed significantly higher density of capillaries than the limb muscles, taken in consideration the muscle cross-sectional area, with the masseter having the highest capillary density ever reported for human sedentary skeletal muscles. Judged from the number of capillaries per muscle fibre, the limb muscles showed the best capillarization. However, since the three muscle groups investigated differed with respect to fibre diameter, our evaluation of number of capillaries per muscle fibre was related also to fibre diameter. Thus, capillary constants were created which take fibre diameter into account. Based on these new parameters, the oro-facial and masseter muscles were found to be relatively better supplied by capillaries than the limb muscles. These results suggest differences in tasks and functional activity between muscles, and reflect a relatively higher need and demand for blood supply in the masticatory and oro-facial muscles than in limb muscles.
8793722
Intermediate filament proteins in TPA-treated skeletal muscle cells in culture.
The cocarcinogenic phorbol ester 13-tetradecanoyl-O-phorbol acetate selectively and reversibly inhibits the ongoing differentiation programme of chick muscle cells in culture. 13-tetradecanoyl-O-phorbol acetate promptly blocks spontaneous contractions in mature myotubes and induces them to retract, forming giant myosacs and concurrently stress fibre-like structures are assembled. Using indirect immunofluorescence to localise desmin, the muscle specific intermediate filament protein, it was shown that its distribution is longitudinally oriented in mature myotubes. In myosacs, desmin has a reticular pattern although not as linearly oriented as in control myotubes. Using gel electrophoresis of control and 13-tetradecanoyl-O-phorbol acetate treated cell extracts, three major protein bands were observed with molecular weight of 43, 50 and 55 kDa. They migrate as actin, desmin and vimentin, respectively. The 50 kDa and 55 kDa proteins were expressed more in 13-tetradecanoyl-O-phorbol acetate-treated cells. The 50 kDa band was confirmed as desmin by immunoblotting using anti-chicken desmin antibody. Two-dimensional gel electrophoresis analysis showed the appearance of more acidic isoforms of the 50 and 55 kDa proteins 13-tetradecanoyl-O- phorbol in acetate-treated cells. The 43 kDa protein was seen as three distinct isoforms in control cells and as only two isoforms in 13-tetradecanoyl-O-phorbol acetatetreated cells.
8793723
Mechanics of feline soleus: I. Effect of fascicle length and velocity on force output.
The aim of the present study was to quantify how fascicle length and velocity modify force production in cat soleus. puterized muscle puller controlled the length and velocity of the whole-muscle. We recorded the force output at the tendon and the length of muscle fascicles using sonomicrometry during whole-muscle isometric and isokinetic contractions. Peak muscle stress was estimated as 31.8 +/- 4.1 N cm-2 (mean and SD) and optimal fascicle length, Lo, was estimated as 3.8 +/- 0.6 cm which corresponds to an optimal ere length of 2.49 +/- 0.08 microns. The isometric force-length data followed closely the expected force-length relationship for cat eres. The force-velocity relationship was found to be similar in shape between cats, but the per cent increment of force over isometric levels for lengthening contractions was highly variable. Estimates of the kinematics of the fascicles based on whole-muscle length were systematically incorrect; whole-muscle velocity was 21% greater than fascicle velocity. The force-velocity data demonstrated consistent dependencies on fascicle length. At lengths below 0.7 Lo (1.74 microns), the shape of the force-velocity relationship was altered by the inclusion of a passive, repulsive force in the estimate of active isometric force. The shape of the force-velocity relationship changed at lengths greater than 0.7 Lo, but was restricted to lengthening velocities where the increment of force with respect to isometric levels was found to increase with fascicle length. This change in shape in the force-velocity relationship for lengthening contractions reveals a systematic, but previously unknown interdependence between fascicle length and velocity on muscle force production.
8793724
Mechanics of feline soleus: II. Design and validation of a mathematical model.
We have developed a mathematical model to describe force production in cat soleus during steady-state activation over a range of fascicle lengths and velocities. The model was based primarily upon a three element design by Zajac but also considered the many different features present in other previously described models. pared quantitatively the usefulness of these features and putative relationships to account for a set of force and length data from cat soleus wholemuscle described in panion paper. Among the novel features that proved useful were the inclusion of a short-length passive force pression, a new normalisation constant for connective-tissue lengths to replace the potentially troublesome slack length, and a new length dependent term for lengthening velocities in the force-velocity relationship. Each feature of this model was chosen to provide the most accurate description of the data possible without adding plexity. Previously described functions pared with novel functions to determine the best description of the experimental data for each of the elements in the model.
8793725
Influences of sarcomere length and selective elimination of myosin filaments on the localization and orientation of triads in rat muscle fibres.
Ultrastructural features of internal membrane systems directly concerned with the excitation-contraction coupling were observed in chemically skinned muscle bundles prepared from Wistar rat extensor digitorum longus muscle to clarify two questions: (1) whether triads localization and orientation are influenced by the ere length and (2) whether triads localisation and orientation are influenced by the selective elimination of myosin filaments. The distance between triads and Z-lines depends on the ere length: it increase with ere length. There is a highly significant (p < 0.01) positive correlation between ere length and the distance between triads and Z-line. The distance between Z-line and triads is dependent on ere length, but the width of junctional gap remains constant when the ere length was changed. Incubation in a concentration of KCI, which dissolves the myosin filaments. The localization and orientation of triads was not altered by the elimination of myosin filaments, however, the distance between the Z-line and triads es shorter when the myosin filaments pletely eliminated. There were significant differences (p < 0.01) between control and myosin filament eliminated fibres in the distances between Z-lines and triads (over 2 microns). These results indicate that the distance between triads and Z-lines depend on the ere length and that there may be some connection(s) between triads and the myofibrils. There is that the ponent responsible for tethering the triads in their normal position is interrupted either because it is normally attached to the myosin filaments, or because it is extracted by the conditions that dissociate myosin filaments.
8793727
Quantitative analysis of sarcomere non-uniformities in active muscle following a stretch.
Electron microscopy of toad (Bufo marinus) muscle fixed without relaxing after a single eccentric contraction at muscle lengths greater than optimum showed over-stretched eres in sufficient numbers to account for more than half of the imposed stretch. Such eres were absent in another muscle fixed without relaxing after an isometric contraction at the same length and largely absent in a third muscle that underwent eccentric contraction at muscle lengths less than optimum. This provides direct evidence in support of the hypothesis that lengthening of muscles at long length involves lengthening of a few half eres to beyond filament overlap, while most half eres are extended much less than in proportion to muscle extension.
8793726
Immunocytochemical localization of caldesmon and calponin in chicken gizzard smooth muscle.
The distribution of caldesmon and calponin in chicken gizzard smooth muscle was investigated with immunofluorescence and immunogold electron microscopy. Immunofluorescence microscopy showed that in verapamil treated (relaxed) muscles the distributions of caldesmon and myosin appeared to be uniform throughout the cytoplasm, but clearly more textured than that of actin filaments as revealed by the distribution of tropomyosin. In shortened muscles both caldesmon and myosin became segregated, in contrast to the distribution of actin, which remained uniform. The distribution of calponin was even more textured, with no similarity to those of caldesmon or myosin. Instead, considerable overlap was observed between calponin and the cytoskeletal protein desmin and, to a lesser extent, beta-actin. By immunogold electron microscopy caldesmon appeared mostly near and around myosin filaments in both relaxed and shortened muscle. Calponin, on the other hand, was found primarily at the periphery of cytoskeletal structures in the same general region as desmin, and very often adjacent to beta-actin, which is mainly in the core. These observations indicated that caldesmon and calponin are associated with different subsets of actin filaments, caldesmon with contractile actin, while calponin with cytoskeletal actin. Thus the in situ localization of caldesmon is consistent with its proposed regulatory function. Calponin, on the other hand, is unlikely to directly regulate actomyosin interactions in these cells; instead, it may function as a bridging protein between the actin and the intermediate filament networks.
8793728
Myosin-based cortical tension in Dictyostelium resolved into heavy and light chain-regulated components.
Cortical tension in most nonmuscle cells is due largely to force production by conventional myosin (myosin II) assembled into the cytoskeleton. Cytoskeletal contraction in smooth muscle and nonmuscle cells is influenced by the degree of myosin filament assembly, and by activation of myosin motor function via regulatory light chain phosphorylation. binant Dictyostelium discoideum cell lines have been generated bearing altered myosin heavy chains, resulting in either constitutive motor function or constitutive assembly into the cytoskeleton. Analysis of these cells allowed stiffening responses to agonists, measured on single cells, to be resolved into an regulatory light ponent reflecting activation of motor function, and a myosin heavy chain ponent reflecting assembly of filaments into the cytoskeleton. These ponents can account for all of the cortical stiffening response seen during tested in vivo contractile events.
8793730
Apoptotic cell death of photoreceptor cells in mice deficient for the adhesion molecule on glia (AMOG, the beta 2- subunit of the Na, K-ATPase).
Disruption of the gene for the adhesion molecule on glia (AMOG, the beta 2-subunit of the Na, K-ATPase) in mice results in swelling and subsequent degeneration of astrocyte endfeet in the brainstem and in cell death of photoreceptor cells in the retina. In the present study, we demonstrate that photoreceptor cells in the mutant develop normally during the first postnatal week. Compared to wild-type mice, a slightly increased density of degenerating photoreceptor cells became apparent in 9-day-old mutants and numerous degenerating photoreceptor cells were present in the retina of 16-day-old AMOG/beta 2-deficient mice. In situ labelling of degenerating cells by terminal dUTP nick end labelling and electron microscopic analysis revealed apoptotic cell death of photoreceptor cells. Massive degeneration of photoreceptor cells in the mutant at postnatal day 16 correlated with elevated levels of glial fibrillary acidic protein in retinal astrocytes and with expression of this protein by Muller cells. No evidence was found for degeneration of other retinal cell types or for glial cell death in the optic nerve. Our observations demonstrate that the pathological death of cells induced by disruption of the AMOG/beta 2 gene results from activation of an intrinsic death program, similar to what has been shown to occur during normal development.
8793729
Carotenoid replacement in Drosophila: freeze-fracture electron microscopy.
Because of the consequent lack of photopigment chromophore, carotenoid/ retinoid (vitamin A) deprivation during the larval period of Drosophila leads to decreased rhodopsin in adult photoreceptors. Decreased density of P-face particles in photoreceptor membrane (rhabdomeric microvilli) is a prominent ultrastructural feature of this rhodopsin deficiency. When adults are fed carotenoid, the rhabdomeric P-face particle density-which reflects the concentration of rhodopsin-increases halfway to the replete control level during the first 12 hours, and is fully restored by 2 days. Based on freeze-fracture replicas, there is a continuity of membrane between rhabdomeric microvilli and the parent retinula cell. That confluence is relevant to turnover of photoreceptive membrane. Microvillar and retinula cell P-face particle densities covary. The relevance of the demonstration of rapid recovery from chromophore depletion is discussed in relation to hypotheses that the chromophore and/or related retinoids regulate opsin gene transcription, and/or post-translational processing and deployment from the endoplasmic reticulum to the rhabdomere.
8793731
Characterization of fluo-3 labelling of dense bodies at the hair cell's presynaptic active zone.
The presynaptic active zone is the critical region of a chemical synapse at which Ca2+ entry provokes neurotransmitter release by exocytotic fusion of synaptic vesicles. To facilitate investigations of synaptic function, we have identified a group of fluorescent substances that label individual active zones in living hair cells. The Ca2+ indicator fluo-3, pound studied in most detail, binds to the presynaptic dense bodies that are characteristic of active zones in hair cells and other cells that tonically release transmitter. The indicator's binding is reversible, with a dissociation constant of approximately 350 microM. Because fluo-3 that is bound to a presynaptic dense body continues to detect Ca2+ with an unaltered dissociation constant, the binding of this substance provides a valuable tool for exploration of the Ca2+ concentration at the site of vesicle fusion.
8793732
Neuronal and synaptic organization of the centromedian nucleus of the monkey thalamus: a quantitative ultrastructural study, with tract tracing and immunohistochemical observations.
The ultrastructure of the centromedian nucleus of the monkey thalamus was analysed qualitatively and quantitatively and projection neurons, local circuit neurons, and synaptic bouton populations identified. Projection neurons were mostly medium-sized, with oval-fusiform or polygonal perikarya, few primary dendrites, and frequent somatic spines; local circuit neurons were smaller. Four basic types of synaptic boutons were distinguished: (1) Small- to medium-sized boutons containing round vesicles (SR) and forming asymmetric contacts, identified as corticothalamic terminals. (2) Heterogeneous medium-sized boutons with asymmetric contacts and round vesicles, similar to the so-called large round (LR) boutons, which were in part of cortical origin. (3) Heterogeneous GAD-positive small- to medium-sized boutons, containing pleomorphic vesicles and forming symmetric contacts (F1 type), which included pallidothalamic terminals. (4) Presynaptic profiles represented by GAD-positive vesicle-containing dendrites of local circuit neurons. Complex synaptic arrangements, serial synapses and triads with LR and SR boutons engaging all parts of projection neuron dendrites and somata, were seen consistently, whereas classical glomeruli were infrequent. LR and SR boutons also established synapses on dendrites of local circuit neurons. F1 boutons established synapses on projection neuron somata, dendrites and initial axon segments. Compared to other previously studied motor-related thalamic nuclei, differences in synaptic coverage between proximal and distal projection neuron dendrites were less pronounced, and the density of synapses formed by local circuit dendrites on projection neuron dendrites was lower. pared to other thalamic nuclei, the overlap of different inputs was higher on monkey centromedian cells, and centromedian inhibitory circuits displayed a different organization.
8793733
Cytoskeletal changes during neurogenesis in cultures of avain neural crest cells.
Neural crest cells are motile and mitotic, whereas their neuronal derivatives are terminally post-mitotic and consist of stationary cell body from which processes grow. The present study documents changes in the cytoskeleton that occur during neurogenesis in cultures of avain neural crest cells. The undifferentiated neural crest cells contain dense bundles of actin filaments throughout their cytoplasm, and a splayed array of microtubules attached to the centrosome. In newly differentiating neurons, the actin bundles are disrupted and most of the remaining actin filaments are reorganized into a cortical layer underlying the plasma membrane of the cell body and processes. Microtubules are more abundant in newly-differentiating neurons than in the undifferentiated cells, and individual microtubules can be seen dissociated from the centrosome. Neuron-specific beta-III tubulin appears in some crest cells prior to cessation of motility and cell division, and expression increases with total microtubule levels during neurogenesis. To investigate how these early cytoskeletal changes might contribute to alterations in morphology during neurogenesis, we have disrupted the cytoskeleton with pharmacologic agents. Microfilament disruption by cytochalasin immediately arrests the movement of neural crest cells and causes them to round-up, but does not significantly change the morphology of the immature neurons. Microtubule depolymerization by nocodazole slows the movement of undifferentiated cells and causes retraction of processes extended by the immature neurons. These results suggest that changes in the actin and microtubule arrays within neural crest cells govern distinct aspects of their morphogenesis into neurons.
8793735
GABA inputs control discharge rate primarily within frequency receptive fields of inferior colliculus neurons.
1. Recent studies have suggested that gamma-aminobutyric acid (GABA) inputs shape monaural and binaural neuronal response properties in the central nucleus of the inferior colliculus (CIC). CIC neurons receive major inhibitory GABAergic projections from missural, and extrinsic sources. Many GABAergic projections now are thought to arise from cells that are tonotopically matched to their CIC targets. 2. We tested the hypothesis that GABA circuits are aligned primarily within the CIC target neuron's excitatory response area and therefore have their greatest effects on discharge rate mainly within that frequency domain. GABA inhibition was examined by recording families of isointensity contours before, during, and after GABAA receptor blockade. Iontophoretic application of bicuculline-methiodide (BMI) was used to block GABAA receptors. Quantitative measures of frequency bandwidth and z-score analysis of discharge rate within the excitatory receptive field were used pare pre- and postdrug conditions. 3. Chinchilla CIC unit response properties were similar to those described for other species, with a high percentage of phasic temporal response patterns and nonmonotonic rate-intensity functions in response to monaural contralateral characteristic frequency (CF) tones. Binaural responses of most CIC neurons showed suppression of contralaterally evoked responses by ipsilateral stimulation. 4. For 85% of CIC neurons, blockade of GABAA inputs was found to increase discharge rate within the excitatory response area. Forty-five percent were classified as near-CF changes and 32% as near-CF and low side. Changes in lateral/flanking inhibition in the absence of near-CF changes were never observed. Forty-one percent of CIC neurons displayed less than a 10% increase in frequency bandwidth at 25-35 dB above threshold with BMI application. 5. These data suggest that GABA inhibition arises primarily from neurons with inhibitory fields aligned with their CIC targets. Thus the effect of the inhibition is primarily contained within or overlapping each target neuron's excitatory response area. CIC GABAergic circuits may function to adjust the gain needed for plex signals over a wide dynamic range.
8793736
Presynaptic or postsynaptic location of receptors for angiotensin II and substance P in the medial solitary tract nucleus.
1. Microinjection of angiotensin (Ang) II or substance P (SP) into the medial nucleus tractus solitarii (nTS) produces similar decreases in arterial pressure and heart rate. We previously reported that some medial nTS neurons responsive to SP were also excited by Ang II, and that Ang II increased the release of SP from medulla slices. Both electrophysiological and anatomic data suggest that the cardiovascular effects of these peptides may be mediated by mon neuronal pathway consisting of SP-containing vagal afferent fibers with presynaptic Ang II receptors that innervate medial nTS neurons with SP receptors. To evaluate the validity of this model, we established the presynaptic or postsynaptic location of the receptors for Ang II and SP that mediate excitation of medial nTS neurons by determining the capacity of each peptide to activate the cell before and after blocking synaptic transmission in rat dorsal medulla slices. 2. Extracellular recordings were obtained from 55 medial nTS neurons responsive to Ang II or SP in 400-microns horizontal slices of the dorsal medulla. Neuronal excitation by Ang II and SP was tested before, during, and after reversal of synaptic blockade with low-Ca2+ (0.2 mM), high Mg2+ (5 mM) artificial cerebrospinal fluid (aCSF). Elimination of synaptically evoked short latency responses of the neuron to current pulses applied to afferent fibers in the solitary tract (TS) documented blockade of synaptic transmission by low-Ca2+ aCSF. In most cases, the basal firing rate of the cell increased slowly during perfusion with low-Ca2+ aCSF and stabilized after approximately 30 min at a higher level of spontaneous activity. Responses to the peptides and TS stimulation were also documented after synaptic blockade had been reversed by adding aCSF containing 2-mM Ca2+. 3. Of the 55 medial nTS neurons, 41 were responsive to Ang II; whereas, 50 of the 55 cells were responsive to SP. The neurons were divided into three subgroups on the basis of their responsiveness to Ang II and SP. Although most neurons were responsive to both Ang II and SP (n = 36), five other cells were excited only by Ang II, and 14 neurons were activated only by SP. Of the 55 neurons, 26 were also responsive to L-glutamate: 14 of 17 cells responsive to both Ang II and SP, all 5 neurons excited by Ang II but not by SP, and 7 of 10 neurons responsive only to SP were also excited by L-glutamate. The latency of the action potentials evoked by TS stimulation was much shorter in those neurons responsive only to Ang II (3.6 ms) than in cells excited by both Ang II and SP (6.8 ms) or responsive only to SP (7.4 ms). 4. In 21 of the 36 medial nTS neurons responsive to both Ang II and SP, Ang II continued to excite the cell when synaptic responses to TS stimulation were prevented by low-Ca2+ aCSF, but had no effect on the firing rate of the other 15 neurons during synaptic blockade. Excitation induced by Ang II was also prevented in two of the five medial nTS neurons responsive only to Ang II when synaptic transmission in the slice was blocked. Low-Ca2+ aCSF failed to prevent excitation by SP or L-glutamate in all medial nTS cells responsive to these agonists (n = 50 and n = 26, respectively). In contrast to these observations in medial nTS neurons, Ang II-induced excitation was not altered during synaptic blockade in any of the six dmnX cells studied. No responses to SP or L-glutamate were blocked in dmnX neurons, as also seen in the medial nTS. 5. When all medial nTS neurons responsive to Ang II were examined, the latencies of the response to TS stimulation were significantly shorter in those neurons with presynaptic Ang II receptors than in the group of cells with postsynaptic receptors. In addition, neurons with presynaptic Ang II receptors were distributed differently within the medial nTS than cells with postsynaptic Ang II receptors.(ABSTRACT TRUNCATED)
8793737
Effect of ibotenic acid lesions of the omnipause neurons on saccadic eye movements in rhesus macaques.
1. Although much is known about the neurons that control saccadic eye movements, the precise manner in which they interact is still uncertain. To test the validity peting models of the pontine saccade generator, neurotoxic lesions were made in the nucleus raphe interpositus (rip), which contains one of the principal types of saccade-related neurons, the omnipause neurons (OPNs). The correlated changes in eye movement were quantified in three juvenile rhesus macaques pared with the results predicted by different models. 2. After the location of the OPNs was mapped, the rip was subjected to sequential, punctate pressure injections of ibotenic acid. The resulting progressive damage was correlated with changes in saccade metrics, including a decrease in peak saccadic velocity and an increase in saccade duration. 3. The damage to rip and presumably to the OPNs was not associated with a change in the animals' ability to maintain steady fixation of a stationary target. 4. The results suggest that Robinson's original local feedback model of saccade generation should be modified. Either a second integrator should be added or the concept of local feedback should be abandoned entirely. 5. The suggestion that the OPNs are primarily responsible for fixation is probably incorrect. OPNs may contribute to fixation stability along with a number of other sources.
8793738
Fast-twitch muscle unit properties in different rat medial gastrocnemius muscle compartments.
1. The effect of muscle unit (MU) localization on physiological properties was investigated within the fast-twitch fatigue-resistant (FR) and fast-fatigable (FF) MU populations of rat medial gastrocnemius (MG) muscle. Single MG MUs were functionally isolated by microdissection of the ventral roots. FR and FF MU properties of the most proximal and distal partments pared. The most proximal and partment are subvolumes of the MG innervated by the most proximal and distal primary nerve branch, respectively. A subsample of the isolated units was glycogen depleted and muscle cross sections were stained for glycogen and myosin-adenosinetriphosphatase. 2. It was shown that proximal FF and FR units reached optimum length for force production at shorter muscle pared with the distal FR and FF units. 3. The fast MUs of the partment had small territories that were located close to and/or within the mixed region (containing type I, IIA, IIX, and IIB fibers) of the muscle. The fast MUs of the partment had greater territories that were located in the more superficial muscle part (containing only type IIX and IIB fibers) and in some cases spanned the entire area of the distal partment. 4. FR and FF MUs consisted of muscle fibers identified histochemically as type IIX and IIB, respectively. 5. Within each of the FR and FF MU populations, MUs that were located in the most proximal partment were more resistant to pared with the units located in the most partment. 6. Cross-sectional fiber areas were smaller for the proximal FR and FF fibers, but specific force did not differ among units. Consequently, when account was taken of the innervation ratio, the proximal FR and FF units produced less force than distal units of the same type. Tetanic forces were 87 +/- 27 (SD) mN (proximal FR), 154 +/- 53 (SD) mN (distal FR), 142 +/- 25 (SD) mN (proximal FF), and 229 +/- 86 (SD) mN (distal FF). 7. The present findings suggest that with increasing demand placed on rat MG during in vivo otion, recruitment is likely to proceed from proximal to distal muscle parts within the FR and FF MU populations.
8793739
Plasticity of dorsal horn cell receptive fields after peripheral nerve regeneration.
1. The tibial and sural nerves were transected and repaired in nine adult cats. The receptive field (RF) properties of dorsal horn neurons were examined at three different intervals (5-6, 9, or 12 mo) after axotomy. The properties examined included RF location, area, and modality convergence. In some cases, discrete areas of the cell's RF were stimulated electrically while the evoked cord dorsum potentials (CDPs) and any intracellularly recorded responses were simultaneously recorded. 2. At the shortest interval following reinnervation, the somatotopic organization in the affected areas of the dorsal horn was lost. Dorsal horn cells that received input primarily from regenerated fibers had large, low-threshold excitatory RFs that contained much of the reinnervated skin. Those cells with RFs restricted to a fraction of the reinnervated skin had ponents of their RFs on the foot dorsum supplied by intact fibers (i.e., superficial peroneal nerve). 3. At longer intervals the somatotopic organization remained scrambled. Dorsal horn cell low-threshold RFs were significantly reduced in size. Many cells exhibited large areas of excitatory subliminal fringe and concise inhibitory RFs. In addition, those cells that responded to peripheral stimuli across a wide range of stimulus intensities (wide-dynamic-range cells) also exhibited plasticity in the relative sizes of their low- and high-threshold RFs. 4. At the shortest recovery time, focal electrical stimulation of the skin within the RF of an impaled cell and simultaneous recordings of the evoked CDPs and postsynaptic potentials revealed that at numerous locations within the initial large RFs, single fibers or small groups of fibers could be electrically activated that were not connected to the dorsal horn cell. At the longer recovery times there was a much higher incidence of connectivity. 5. These results suggest that mechanisms affecting both synaptic efficacy of afferent fiber connections and/or the establishment of afferent-driven inhibitory inputs may effect the reshaping of dorsal horn cell RFs after reinnervation. These results are discussed in relation to their potential contribution to previously observed cortical plasticity and functional recovery following similar lesions.
8793740
Properties of the nociceptive neurons of the leech segmental ganglion.
1. The electrical responses of nociceptive (N) lateral and N medial neurons of the leech segmental ganglion to mechanical, chemical, and thermal stimulation of the skin were studied in a superfused ganglion-body wall preparation. 2. Mechanical indentation of the skin > 10 mN evoked in both types of cells a sustained discharge of impulses; afterdischarge was often observed with suprathreshold stimulations. 3. Application to the cutaneous receptive area of 10-100 mM acetic acid or of NaCI crystals and solutions also elicited a firing response in N medial and N lateral cells. In contrast, capsaicin applied to the skin (3.3 x 10(-5) to 3.3 x 10(-2) M) excited N lateral but not N medial neurons. Likewise, impulse discharges were obtained when capsaicin was applied to the cell bodies of N lateral but not of N medial neurons. 4. In both types of N neurons, heating of the skin above 39 degrees C evoked a discharge of impulses whose frequency was roughly proportional to temperature values. 5. Application of repeated suprathreshold heating cycles at 10-min intervals enhanced the impulse frequency of the response (sensitization). Shorter time intervals between heating cycles depressed the response to heat. Sensitization could not be obtained by equivalent soma depolarizations obtained by intracellular current injection. 6. Impulse discharges evoked by irritant agents were also augmented by previous application of noxious heat. 7. N lateral neurons fired in response to low-pH solutions and capsaicin directly applied onto the ganglion. N medial neurons responded inconsistently to acid and were insensitive to capsaicin. Action potentials evoked in N lateral cells by capsaicin had a slow rise, a prominent hump, and a prolonged afterhyperpolarization. 8. It is concluded that N neurons of the leech segmental ganglion respond to different modalities of noxious stimuli applied to their peripheral receptive fields and develop sensitization after repeated noxious stimulation. These properties are typical of mammalian polymodal nociceptors; thus N neurons may be a simple model for analysis of membrane mechanisms associated with polymodality of nociceptive neurons.
8793741
Coding of time-varying electric field amplitude modulations in a wave-type electric fish.
1. The coding of time-varying electric fields in the weakly electric fish, Eigenmannia, was investigated in a quantitative manner. The activity of single P-type electroreceptor afferents was recorded while the amplitude of an externally applied sinusoidal electric field was stochastically modulated. The amplitude modulation waveform (i.e., the stimulus) was reconstructed from the spike trains by mean square estimation. 2. From the stimulus and the reconstructions we calculated the following: 1) the signal-to-noise ratio and thus an effective temporal bandwidth of the units; 2) the coding fraction, i.e., a measure of the fraction of the time-varying stimulus encoded in single spike trains; and 3) the mutual information provided by the reconstructions about the stimulus. 3. Signal-to-noise ratios as high as 7:1 were observed and the bandwidth ranged from 0 up to 200 Hz, consistent with the limit imposed by the sampling theorem. Reducing the cutoff frequency of the stimulus increased the signal-to-noise ratio at low frequencies, indicating a nonlinearity in the receptors' response. 4. The coding fraction and the rate of mutual information transmission increased in parallel with the standard deviation (i.e., the contrast) of the stimulus as well as the mean firing rate of the units. Significant encoding occurred 20-40 Hz above the spontaneous discharge of a unit. 5. When the temporal cutoff frequency of the stimulus was increased between 80 and 400 Hz, 1) the coding fraction decreased, 2) the rate of mutual information transmission remained constant over the same frequency range, and 3) the reconstructed filter changed. This is in agreement with predictions obtained in a simplified neuronal model. 6. Our results suggest that 1) the information transmitted by single spike trains of primary electrosensory afferents to higherorder neurons in the fish brain depends on the contrast and the cutoff frequency of the stimulus as well as on the mean firing rate of the units; and 2) under optimal conditions, more than half of the information about a Gaussian stimulus that can in principle be encoded is carried in single spike trains of P-type afferents at rates up to 200 bits per second.
8793742
Enhancement by lanthanide of general anesthetic-induced GABAA-receptor current in rat septal cholinergic neurons in culture.
1. Actions of lanthanide ions were examined on general anesthetic-induced currents mediated by the activation of gamma-aminobutyric acid-A receptors (GABAARs) in rat septal cholinergic neurons in primary culture, by means of a whole cell voltage-clamp technique. 2. La3+ enhanced a pentobarbital sodium (500 microM)-induced GABAAR current in a reversible and dose-dependent manner (median effective concentration = 15.7 microM; Hill coefficient = 1.58; 89% increase by 100 microM La3+). This action was independent of holding potentials (-34-26 mV), and was due to an increase in the apparent affinity for pentobarbital (295% increase with 100 microM La3+). 3. The action of La3+ on pentobarbital current was mimicked particularly by other lanthanide ions (Ce3+, Nd3+, Gd3+, Tb3+, Er3+, and Yb3+) and by Y3+ among a number of multivalent cations. There was no correlation between the potentiated proportions by lanthanide ions and their crystal ionic radii. 4. La3+ (100 microM) also augmented a GABAAR response evoked by either alpha-chloralose (500 microM), 2,6-diisopropylphenol (50 microM), or 3-alpha-hydroxy-5-alpha-pregnane-11,20-dione (20 microM) (144, 80, and 153% increase, respectively). 5. We suggest that the GABAAR channels on septal neurons are endowed with a novel "lanthanide site" whose activation results in a positive allosteric interaction with a binding site of the general anesthetics that is involved in a direct activation of GABAAR channels without any added exogenous GABA.
8793743
Glycine-evoked currents in acutely dissociated neurons of the guinea pig ventral cochlear nucleus.
1. Glycine was applied to acutely dissociated neurons of the guinea pig ventral cochlear nucleus (VCN) with the use of iontophoresis. With approximately equal chloride concentrations in the extra- and intracellular solutions (i.e., chloride equilibrium potential = 0 mV), cells held at -60 mV responded with inward currents that were 1-10 nA in amplitude, had rise times of approximately 50 ms, and decayed to half of the peak amplitude in 50-600 ms. More than 95% of cells with diameters > 12 microns responded to glycine. Response amplitude and area increased with increasing duration of the iontophoretic pulse. Response amplitude saturated at pulse durations of 60-80 ms, whereas response area did not exhibit saturation for pulse durations of 10-100 ms. 2. The glycine antagonist strychnine was added to the extracellular solution at concentrations of 0.5-500 nM to evaluate its effect on glycine-evoked responses. Strychnine produced a 50% reduction in the response at a concentration of 12 nM and the dose-response function had a limiting slope (Hill coefficient) of 1.4. 3. Changes in glycine-evoked currents as a function of cell membrane potential were examined in the presence of tetrodotoxin, tetraethylammonium chloride, and 4-aminopyridine, which block sodium and potassium conductances activated by depolarization. Both the amplitude and the decay of glycine-evoked currents displayed a voltage dependence. Under conditions where the glycine currents reversed at -35 mV, the amplitudes of responses evoked at membrane potentials of 0 mV were 2.3 times larger than those of responses evoked at -70 mV. The decay time constant at 0 mV was 1.49 times longer than that at -70 mV. 4. Acutely dissociated neurons of the VCN previously have been classified on the basis of the absence (type I) or presence (type II) of a low-threshold outward current. Type I cells fire repetitively in response to current pulses, whereas type II cells fire transiently. Glycine-evoked responses pared in cells identified electrophysiologically as type I or type II on the basis of previously established criteria under voltage clamp. The average amplitudes of responses recorded at a membrane potential of -70 mV were 1.1 and 1.3 nA for type I and type II cells, respectively. The rise time of the glycine current for the two groups of cells was similar (52 ms for type I and 57 ms for type II), but the decay of currents to half-maximum amplitude following the offset of the iontophoretic pulse was longer in type II cells (340 ms) than in type I cells (173 ms). No differences between the two groups were noted with regard to the outward rectification of peak currents or the voltage dependence of current decay. 5. The reversal potential of glycine-evoked responses was determined in extracellular solutions with varying chloride concentrations. The change in the glycine reversal potential (54 mV) for a 10-fold change in chloride concentration was similar to the change in the chloride equilibrium potential (58 mV) over the same range of extracellular chloride concentrations. A similar result was obtained by maintaining the extracellular chloride concentration constant and varying the chloride concentration in the intracellular solution. Glycine-evoked responses were not affected by changes in the potassium or sodium equilibrium potentials. The glycine receptors are therefore principally permeable to chloride. 6. In the VCN, glycine-mediated currents are readily evoked from the majority of larger neurons, indicating an abundance of glycine receptors on the somata and proximal processes of these neurons. The properties of glycine receptors in VCN and other areas of the nervous system are generally similar. The voltage dependence of glycine-evoked currents implies that the inhibitory effectiveness of glycine receptors in VCN increases nonlinearly with depolarization.
8793744
Distribution and functional properties of glutamate receptors in the leech central nervous system.
1. The effect of kainate and other glutamatergic agonists on the membrane potential (Em), the intracellular Na+ activity (aNai), and the intracellular free Ca2+ concentration ([Ca2+]i) of identified leech neurons and neuropile glial cells was measured with conventional and ion-sensitive microelectrodes, as well as with the use of the iontophoretically injected fluorescent indicators sodium-binding benzofuran isophthalate and Fura-2. 2. In Retzius neurons, AE, L, 8, and 101 motoneurons, and in the unclassified 50 neurons (Leydig cells) and AP neurons, as well as in neuropile glial cells, bath application of 100 microM kainate evoked a marked membrane depolarization and an increase in aNai and [Ca2+]i. The kainate-induced aNai increase persisted in solutions with high Mg2+ concentration in which synaptic transmission is blocked. 3. A membrane depolarization as well as an increase in aNai and [Ca2+]i was also evoked by L-glutamate, quisqualate, and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). The agonist-induced [Ca2+]i increase was inhibited by 6,7-dinitroquinoxaline-2,3-dione (DNQX). 4. In Ca(2+)-free solution, the kainate-induced [Ca2+]i increase was abolished in the neurons and in neuropile glial cells, whereas membrane depolarization and aNai increase were unchanged. In Na(+)-free solution, kainate had no effect on Em, aNai, or [Ca2+]i in the neurons. 5. In the mechanosensory T, P, and N neurons, kainate induced considerably smaller membrane depolarizations than in the other neurons or in neuropile glial cells, and it had no significant effect on aNai or [Ca2+]i. 6. It is concluded that in leech segmental ganglia the majority of the neurons and the neuropile glial cells, but probably not the mechanosensory neurons, possess glutamate receptors of the AMPA-kainate type. In the neurons, the [Ca2+]i increase caused by glutamatergic agonists is due to Ca2+ influx through voltage-dependent Ca2+ channels that are activated by the agonist-induced membrane depolarization.
8793745
AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide.
1. The kinetics of onset of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization by glutamate, and the extent of attenuation of AMPA receptor desensitization by cyclothiazide, showed pronounced cell-to-cell variation in cultures of rat hippocampal neurons. Cultures prepared from area CA1 stratum radiatum tended to show weaker modulation by cyclothiazide than cultures prepared from the whole hippocampus. 2. Kinetic analysis of concentration jump responses to glutamate revealed multiple populations of receptors with fast (approximately 400 ms), intermediate (approximately 2-4 s), and slow (> 20 s) time constants for recovery from modulation by cyclothiazide. The amplitudes of ponents varied widely between cells, suggesting the existence of at least three populations of AMPA receptor subtypes, the relative density of which varied from cell to cell. 3. plex patterns of sensitivity to cyclothiazide seen in hippocampal neurons could be reconstituted by assembly of binant AMPA receptor subunits generated from cDNAs encoding the flip (i) and flop (o) splice variants of the GluR-A and GluR-B subunits. Recovery from modulation by cyclothiazide was slower for GluR-AiBi and GluR-AoBi than for GluR-AiBo and GluR-AoBo. 4. Coexpression of the flip and flop splice variants of GluR-A, in the absence of GluR-B, revealed that heteromeric AMPA receptors with intermediate sensitivity to cyclothiazide, similar to responses observed for binations GluR-AoBi or GluR-AiBo, could be generated independently of the presence of the GluR-B subunit. However, recovery from modulation by cyclothiazide was twofold slower for GluR-AiBi than for homomeric GluR-Ai, indicating that the GluR-A and GluR-B subunits are not functionally equivalent in controlling sensitivity to cyclothiazide. 5. These results demonstrate that AMPA receptors expressed in hippocampal neurons are assembled in a variety of subunit and splice binations that might serve as a mechanism to fine-tune the kinetics of synaptic transmission.
8793746
Unified theory regarding A/P and M/L balance in quiet stance.
1. Control of posture in quiet stance has been quantified by center of pressure (COP) changes in the anterior-posterior (A/P) and medial-lateral (M/L) directions from a single force platform. Recording from a single force platform, researchers are unable to recognize two separate mechanisms that e evident when two force platforms are used. Depending on the stance position taken, binations of an ankle mechanism and a hip (load/unload) mechanism are evident. In side-by-side stance, A/P balance is totally under ankle (plantar/dorsiflexor) control, whereas M/L balance is under hip (abductor/adductor) control. In tandem stance, the A/P balance is dominated by the hip mechanism, with mixed and small or sometimes negligible contributions by the ankle plantar/dorsiflexors: for M/L balance, the reverse is evident; ankle invertors/evertors dominate, with mixed and small contribution from the hip load/unload mechanism. In an intermediate 45 degrees stance position, both ankle and hip mechanisms contribute to the net balance control in totally different ways. In the M/L direction the two strategies reinforce, whereas in the A/P direction the ankle mechanism must e and cancel most of the inappropriate contribution by the hip load/unload mechanism. A spatial plot of the separate mechanisms reveals the fact that the random-looking COP scatter plot is nothing more than a spatial and temporal summation of two separate spatial plots. A straight line joining the individual COPs under each foot is the load/unload line controlled by the hip mechanism. At right angles to this load/unload line in the side-by-side and tandem positions is the independent control line by the ankle muscles. In an intermediate standing position, the separate control lines exist, but now the ankle control is not orthogonal to the load/unload line; rather, it acts at an angle of approximately 60 degrees. The direction of these ankle control and load/unload lines also allows us to pinpoint the muscle groups responsible at the ankle and hip in any of the stance positions.
8793747
Modulation of spinal visceral nociceptive transmission by NMDA receptor activation in the rat.
1. Thirty-three neurons in the L6-Sl spinal cord of 30 adult male Sprague-Dawley rats were characterized for responses to colorectal distention (CRD, 20-80 mmHg, 20 s) and convergent cutaneous receptive fields in the presence and absence of N-methyl-D-aspartate (NMDA; 1 microM) or D-serine (1 microM) administered locally by pressure ejection. 2. NMDA ejected locally increased the resting (spontaneous) activity, responses to CRD, postdistention afterdischarges, encoding of visceral nociception, and the size of convergent cutaneous receptive fields of some neurons. Facilitation of responses to noxious intensities of CRD (> or = 40 mmHg) was apparent between 30 s and 4 min after drug ejection. The slope of stimulus-response functions to graded intensities of CRD was increased significantly by NMDA, although mean response threshold was not significantly altered after NMDA ejection. 3. Facilitatory effects of NMDA on responses to CRD and increases in size of convergent cutaneous receptive fields were blocked or reversed by administration of the NMDA receptor antagonist, 5-amino-2-phosphono-valeric acid. 4. D-serine, an agonist at the glycine modulatory site on the NMDA plex, generally mimicked the effects of NMDA on neurons responsive to CRD. The effects of D-serine were blocked by the glycine site antagonist 7-chloro-kynurenic acid (7-CK). 7-CK also blocked NMDA-produced effects on responses to CRD and increases in size of cutaneous receptive fields. 5. No differences were found between spinal neurons with and without documented long ascending projections with respect to effects of NMDA or D-serine. 6. These findings demonstrate involvement of spinal NMDA receptors in mediating hyperexcitability of spinal neurons to visceral nociceptive input and suggest an important contribution of spinal NMDA receptors in visceral hyperalgesic syndromes.
8793748
Role of voltage-gated calcium channels in the generation of activity-induced extracellular pH transients in the rat hippocampal slice.
1. The role of voltage-gated calcium channels in the generation of activity-induced alkaline shifts in extracellular pH (pHo) was studied in rat hippocampal slices (area CAI) by means of Ca(2+)-and H(+)-selective microlectrodes inserted into the stratum pyramidale and/or stratum radiatum. 2. plete pharmacological blockade of ionotropic glutamate receptors and gamma-aminobutyric acid-A (GABAA) receptors, trains (5-10 Hz, 5-10s) of antidromic spikes in pyramidal neurons were associated with a fast alkaline transient of up to 0.17 pH units and a fall in the extracellular Ca2+ concentration ([Ca2+]o). The alkaline shift was strongly enhanced upon inhibition of extracellular carbonic anhydrase. 3. Application of 100 microM Ni2+ plus 100 microM Cd2+ inhibited both the fall in [Ca2+]o and the alkaline transient triggered by antidromic spikes. The alkaline shift was abolished in the absence of extracellular Ca2+. 4. In the absence of postsynaptic receptor antagonists, alkaline transients linked to a given level of synaptic excitation in s. radiatum were strongly suppressed after blockade of somatic (and, consequently, of dendritic "backpropagating") spikes by microdrop application of tetrodotoxin to the cell-body layer. 5. We have previously shown that activity-induced alkaline transients in the CAI region are due to an influx of Ca2+ into neurons, which triggers an influx of H+ ions probably caused by activation of a plasmalemmal Ca2+/H+ ATPase. The present results indicate that much (in s. pyramidale perhaps all) of the pH-changing influx of Ca2+ is mediated by voltage-gated Ca2+ channels.
8793749
EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in response to bradykinin and heat.
1. Our previous studies, in which we used in vitro canine testispermatic nerve preparations, showed that prostaglandin E2 (PGE2) augments both bradykinin (BK)- and heat-induced discharges of polymodal receptors. However, the PGE2 concentration required to augment the BK responses were 100 times lower than those necessary for the heat responses, suggesting that different receptors are involved in these phenomena. We studied which receptors for E series of prostaglandins (EP receptors) were responsible, using the antagonist and agonists for three subtypes of EP receptors. 2. PGE2-induced augmentation of the BK responses was unaffected when treated with an antagonist for the EP1 receptor, AH6809. 3. An agonist for the EP3 receptor, M&B28767, at > or = 10 nM, significantly augmented the BK responses in a concentration-dependent manner that mimics the PGE2-induced effect. An agonist for the EP1 receptor, 17-phenyl trinor PGE2 (17-phen PGE2), at the high concentrations of 0.1 and 1 microM, augmented the BK responses in two and four of nine cases tested, respectively. However, this augmentation was not suppressed by the antagonist for the EP1 receptor, AH6809. In addition, an agonist for the EP2 receptor, butaprost, did not affect the BK responses even when applied at 10 microM. 4. In contrast, butaprost at > or = 10 nM significantly augmented the heat responses in a concentration-dependent manner. M&B28767 and 17-phen PGE2, respectively, augmented the heat responses at higher concentrations of 100 nM and 1 microM. 5. These results indicate that the EP3 and EP2 receptor subtypes are differentially implicated in the respective PGE2-induced augmentation of BK responses and heat responses of polymodal receptors.
8793750
Gustatory neural coding in the monkey cortex: mixtures.
1. Psychophysicists have shown that the intensity and quality of a taste stimulus, as perceived by humans, is modified by including that stimulus in a mixture. Gustatory neurons in the primary taste cortex (anterior insula and frontal operculum) of the cynomolgus macaque are involved with the coding of stimulus intensity and quality, and so should reflect the impact of these stimulus interactions. 2. We recorded the activity of 48 neurons in primary taste cortex in response to the oral application of each of the four basic stimuli, their six possible dyads, the four triads, and the tetrad of all four. Stimuli were maintained at a constant intensity in all mixtures by increasing their concentrations as the number ponents rose. 3. Glucose was the most effective basic stimulus, followed by quinine HCl, NaCl, and HCl. The mean response to dyads was suppressed by 50% from the sum of responses to the two ponents. The response to triads was 62% lower than the sum of responses to their ponents, and activity evoked by the tetrad was suppressed by 74% from the sum of all four individual responses. Therefore there was nearly total suppression in the sense that the responses to the mixtures were approximately 1/2, 1/3, and 1/4 the sums of responses to two, three, and ponents, respectively. 4. Neurons could be divided into four subtypes: those that responded best to each of the basic stimuli. All subtypes except HCl cells were about equally suppressed when their preferred stimulus was included in a mixture. HCl was a particularly ineffective stimulus, such that this subtype responded poorly and so was less susceptible to mixture suppression. 5. Taste quality, as indexed by correlation coefficients among profiles of activity, was quite predictable for dyads. If the mixture included HCl, the profile it generated correlated poorly (about +0.20) with that of HCl and rather well (about +0.60) with that of the ponent. If HCl was not included, the mixture's profile correlated about +0.40 with that of ponent. 6. The profile generated by the mixture of three stimuli was predictable only if one of ponents was HCl. In that case, the triad elicited a profile midway between those of the other ponents, i.e., the contribution of HCl was largely ignored. When HCl was not involved, or when all four basic stimuli bined, the resulting profiles were poorly correlated with those of all basic stimuli. 7. The contribution made by each basic taste to human perception and to the macaque's neurophysiological response pared for all mixtures. The contribution was often quite similar for human and macaque, but when differences occurred, they were typically due to lower activity from HCl cells in the macaque, a loss that was replaced mainly by larger responses from glucose neurons. 8. The magnitude of responses to mixtures in the macaque taste cortex matches well with expectations from human psychophysical studies. The presumed quality of the response to mixtures is also similar, except that HCl is less effective in monkeys and sugars more so.
8793751
Effects of dopamine on postural control in parkinsonian subjects: scaling, set, and tone.
1. This study investigates the effects of parkinsonism and of dopamine replacement therapy (levodopa) on scaling the magnitude of automatic postural responses based on sensory feedback and on predictive central set. Surface reactive torques and electromyographic (EMG) activity in response to backward surface translations pared in patients with parkinsonism ON and OFF levodopa and in elderly control subjects. Correlations between the earliest postural responses [initial rate of change of torque and integrated EMG (IEMG)] and translation velocity provided a measure of postural magnitude scaling using somatosensory feedback. Correlations of responses with expected translation amplitude provided a measure of scaling dependent on predictive central set because the responses preceded pletion. 2. Parkinsonian EMG responses in six leg and trunk muscles were not later than in elderly control subjects. In fact, quadriceps antagonist latencies were earlier than normal, resulting in coactivation at the knee not present in control subjects. EMG activation was fragmented, with short burst durations and high tonic levels that often returned to baseline with multiple bursts. In addition, parkinsonian responses showed smaller-than-normal agonist extensor bursts and larger-than-normal activation in tibialis and rectus femorus antagonist flexors. 3. Although parkinsonian subjects scaled postural responses to both displacement velocities and amplitudes, their torque response were smaller than those of elderly controls, especially in response to the largest displacement amplitudes. The gain (slope) of postural response magnitude scaling to displacement velocity was similar for parkinsonian and control subjects, although parkinsonian subjects had smaller torques. Parkinsonian subjects were also able to use prediction to scale responses to small expected displacement amplitudes, but many patients did not generate the larger plantarflexion torques required at larger displacement amplitudes. Reduced torque at large amplitudes was associated with less agonist gastrocnemius IEMG, increased tibialis antagonist burst responses, and increased tibialis tonic background activity. 4. Levodopa further reduced the already low magnitude of initial torque and IEMG responses to displacement velocities and amplitudes in parkinsonian patients. The ability to scale postural responses to velocity feedback was not affected by levodopa, but the ability to scale responses to large displacement amplitudes based on central set was worsened by levodopa. Levodopa also significantly reduced the tonic, background levels of EMG, particularly the distal gastrocnemius and tibialis activity. 5. High baseline muscle tone was apparent in parkinsonian subjects from their high background EMG activity in quiet stance, especially in tibialis and quadriceps, and the slow initial velocity of center of mass falling in response to displacements. By reducing tone, levodopa reduced passive stiffness to perturbations without increasing EMG burst magnitudes, resulting in less resistance to external displacements and thus faster center of body mass (COM) displacements. 6. The biggest postural deficit in parkinsonian subjects was not in response latency, pattern, or reactive or predictive scaling of response magnitude, but in quickly generating an adequate level of postural force. Dopamine improved tonic background postural tone but further weakened automatic postural responses to external displacements. Thus the basal ganglia may participate in postural control by regulating appropriate levels of background postural tone and by enabling adequate force generation for resisting external displacements.
8793752
Characterization of TTX-resistant persistent Na+ current underlying pacemaker potentials of fish gonadotropin-releasing hormone (GnRH) neurons.
1. Endogenous pacemaker activities are important for the putative neuromodulator functions of the gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN) cells. Previously we have shown by current-clamp analysis that a tetrodotoxin (TTX)-resistant persistent Na+ current, INa(slow), plays an important role in the generation of pacemaker potentials of TN-GnRH cells. The present study investigates electrophysiological characteristics of INa(slow) by using the whole cell patch-clamp technique in in vitro whole-brain preparation of a small fish brain. 2. TN-GnRH cells lie immediately beneath the ventral meningeal membrane; the cells could thus be exposed and visualized by gently removing the meningeal membrane. INa(slow) currents were isolated pharmacologically by blocking K+ currents, Ca2+ currents, and conventional fast Na+ currents. 3. INa(slow) was characterized by resistance to TTX blockade, dependence on external Na+, slow activation, very slow and little inactivation, and wide overlap of activation and inactivation curves near the resting potential. These characteristics are distinct from those of conventional fast Na+ current, and are relevant for the generation of persistent inward currents necessary for the pacemaker activity of TN-GnRH cells.
8793753
Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation.
1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration ponents along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated plete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these ponents in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties that could be characterized as the low-frequency range of "translational" otolith-ocular reflexes; and 2) response vectors associated with an eye position modulation in phase with head position ("tilt" otolith-ocular reflexes). 4. The responses associated with two otolith-ocular vectors with pronounced dynamics consisted of horizontal eye movements evoked as a function of gravity along the interaural axis and vertical eye movements elicited as a function of gravity along the vertical head axis. Both responses were characterized by a slow-phase eye velocity sensitivity that increased three- to five-fold and large phase changes of approximately 100-180 degrees between 0.02 and 0.51 Hz. These dynamic properties could suggest nontraditional temporal processing in utriculoocular and sacculoocular pathways, possibly involving spatiotemporal otolith-ocular interactions. 5. The two otolith-ocular vectors associated with eye position responses in phase with head position (tilt otolith-ocular reflexes) consisted of torsional eye movements in response to gravity along the interaural axis, and vertical eye movements in response to gravity along the nasooccipital head axis. These otolith-ocular responses did not result from an otolithic effect on slow eye movements alone. Particularly at high frequencies (i.e., high speed rotations), saccades were responsible for most of the modulation of torsional and vertical eye position, which was relatively large (on average +/- 8-10 degrees/g) and remained independent of frequency. Such reflex dynamics can be simulated by a direct coupling of primary otolith afferent inputs to the oculomotor plant. (ABSTRACT TRUNCATED)
8793754
Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. II. Inertial detection of angular velocity.
1. The dynamic contribution of otolith signals to three-dimensional angular vestibuloocular reflex (VOR) was studied during off-vertical axis rotations in rhesus monkeys. In an attempt to separate ponents to head velocity from those to head position relative to gravity during low-frequency sinusoidal oscillations, large oscillation amplitudes were chosen such that peak-to-peak head displacements exceeded 360 degrees. Because the waveforms of head position and velocity differed in shape and frequency content, the particular head position and angular velocity sensitivity of otolith-ocular responses could be independently assessed. 2. During both constant velocity rotation and low-frequency sinusoidal oscillations, the otolith system generated two different types of oculomotor responses: 1) modulation of three-dimensional eye position and/or eye velocity as a function of head position relative to gravity, as presented in the preceding paper, and 2) slow-phase eye velocity as a function of head angular velocity. These two types of otolith-ocular responses have been analyzed separately. In this paper we focus on the angular velocity responses of the otolith system. 3. During constant velocity off-vertical axis rotations, a steady-state nystagmus was elicited that was maintained throughout rotation. During low-frequency sinusoidal off-vertical axis oscillations, dynamic otolith stimulation resulted primarily in a reduction of phase leads that characterize low-frequency VOR during earth-vertical axis rotations. Both of these effects are the result of an internally generated head angular velocity signal of otolithic origin that is coupled through a low-pass filter to the VOR. No change in either VOR gain or phase was observed at stimulus frequencies larger than 0.1 Hz. 4. The dynamic otolith contribution to low-frequency angular VOR exhibited three-dimensional response characteristics with some quantitative differences in the different ponents. For horizontal VOR, the amplitude of the steady-state slow-phase velocity during constant velocity rotation and the reduction of phase leads during sinusoidal oscillation were relatively independent of tilt angle (for angles larger than approximately 10 degrees). For vertical and torsional VOR, the amplitude of steady-state slow-phase eye velocity during constant velocity rotation increased, and the phase leads during sinusoidal oscillation decreased with increasing tilt angle. The largest steady-state response amplitudes and smallest phase leads were observed during vertical/torsional VOR about an earth-horizontal axis. 5. The dynamic range of otolith-borne head angular velocity information in the VOR was limited to velocities up to approximately 110 degrees/s. Higher head velocities resulted in saturation and a decrease in the amplitude of the steady-state ponents during constant velocity rotation and in increased phase leads during sinusoidal oscillations. 6. The response characteristics of otolith-borne angular VORs were also studied in animals after selective semicircular canal inactivation. Otolith angular VORs exhibited clear low-pass filtered properties with a corner frequency of approximately 0.05-0.1 Hz. Vectorial summation of canal VOR alone (elicited during earth-vertical axis rotations) and otolith VOR alone (elicited during off-vertical axis oscillations after semicircular canal inactivation) could not predict VOR gain and phase during off-vertical axis rotations in intact animals. This suggests a plex interaction of semicircular canal and otolith signals. 7. The results of this study show that the primate low-frequency enhancement of VOR dynamics during off-vertical axis rotation is independent of a simultaneous activation of the vertical and torsional "tilt" otolith-ocular reflexes that have been characterized in the preceding paper. (ABSTRACT TRUNCATED)
8793755
Changes in the response properties of neurons in the ventroposterior lateral thalamic nucleus of the raccoon after peripheral deafferentation.
1. Single neurons in the ventroposterior lateral thalamic nucleus were studied in 10 anesthetized raccoons, 4 of which had undergone amputation of the fourth digit 4-5 mo before recording. Neurons with receptive fields on the glabrous skin of a forepaw digit were examined in response to electrical stimulation of the "on-focus" digit that contained the neuron's receptive field and stimulation of an adjacent, "off-focus" digit. 2. In normal raccoons all neurons responded to on-focus stimulation with an excitation at a short latency (mean 13 ms), whereas only 63% of the neurons responded to off-focus digit stimulation. The off-focus responses had a longer latency (mean 27.2 ms) and a higher threshold than the on-focus responses (800 and 452 microA, respectively). Only 3 of 32 neurons tested with off-focus stimulation had both a latency and a threshold within the range of on-focus values. Inhibition following the excitation was seen in the majority of neurons with both types of stimulation. 3. In the raccoons with digit removal, the region of the thalamus that had lost its major peripheral input (the "deafferented" region) was distinguished from the normal third and fifth digit regions on the basis of the sequence of neuronal receptive fields within a penetration and receptive field size as described previously. 4. Almost all of the neurons in the deafferented region (91%) were excited by stimulation of one or both adjacent digits. The average latency for these responses was shorter (15.3 ms) and the threshold was lower than was the case with off-focus stimulation in control animals. These values were not significantly different from the responses to on-focus stimulation in the animals with digit amputation. 5. These results confirm that reorganization of sensory pathways can be observed at the thalamic level. In addition to the changes in the somatotopic map that have been shown previously with the use of mechanical stimuli, the present paper demonstrates an improvement in several quantitative measures of single-unit responses. Many of these changes suggest that this reorganization could be explained by an increased effectiveness of preexisting, weak connections from the off-focus digits; however, the increase in the proportion of neurons responding to stimulation of adjacent digits may indicate that sprouting of new connections also occurs.
8793756
Synaptic structural complexity as a factor enhancing probability of calcium-mediated transmitter release.
1. In a model synaptic system, the excitatory neuromuscular junction of the freshwater crayfish, the nerve terminals possess synapses that vary in plexity, with numbers of active zones ranging from zero to five. Active zones on individual synapses show a wide range of separation distances. We tested the hypothesis that two active zones of a single synapse in close proximity can enhance the localized increase in free calcium ion concentration, thus enhancing the probability of neurotransmission at that synapse. We evaluated the increase in calcium ion concentration as a function of distance between adjacent active zones. 2. To test this hypothesis, a reaction-diffusion model for Ca2+ entering the presynaptic terminals was used. This test was used because 1) present measurement techniques are inadequate to resolve quantitatively the highly localized, transient calcium microdomains at synaptic active zones; and 2) there is presently no suitable preparation for physiological recording from isolated synapses with varying distances between active zones. Included in the model were intracellular buffer and a typical distribution of voltage-activated Ca2+ channels for an active zone, estimated from freeze-fracture micrographs. 3. The model indicated that localized Ca2+ clouds from discrete active zones can overlap to create spatial enhancement of Ca2+ concentration. The degree of interaction between two active zones depends on the distance between them. When two typical active zones are separated by < or = 200 nm, the maximum intracellular Ca2+ concentration ([Ca2+]i) is greater at 1) the midpoint between them, and 2) the center of each one, than at the corresponding positions for a single isolated active zone. Enhanced [Ca2+]i at the edge of the active zone where "docked" synaptic vesicles occur would be expected to have an effect on transmitter release. 4. When the model includes no intracellular buffer, the increase in [Ca2+]i is a linear function of calcium channel current, but is a nonlinear function of the number of conducting calcium channels in an active zone. With immobile buffer included, the increase in [Ca2+]i is nonlinear with respect to both channel current and number of conducting channels. 5. Inclusion of immobile buffer in the model provides "released" residual calcium that slowly accumulates during a train of current pulses. Released residual calcium accumulates more rapidly at paired active zones separated by < or = 200 nm that at single isolated active zones. 6. We propose that the probability of release is enhanced at synapses with closely associated active zones. Synapses of this type plex" synapses) could be selectively recruited when the neuron is active at low frequencies. At higher frequencies of neuronal activity, more distant active zones may interact and acquire a greater probability of releasing quanta. This would provide the nerve terminal with ponent of a mechanism for frequency facilitation, because the number of quanta released by the terminal as a whole would increase with frequency. Thus variation in plexity in a nerve terminal provides a mechanism for short-term plasticity of transmitter release.
8793757
Oscillatory firing and interneuronal correlations in squirrel monkey striate cortex.
1. This work explores a mechanism that the brain may use for linking related percepts. It has been proposed that temporal relationships in the firing of neurons may be important in indicating how the stimuli that activate those neurons are related in the external world. Such temporal relationships cannot be seen with conventional receptive field mapping but require cross-correlation and auto-correlation analysis. 2. In the cat and the macaque monkey, cells with similar receptive field properties show correlated firing even when their receptive fields do not overlap. Here I report that in the squirrel monkey, as in the cat, pairs of cells < or = 5 mm apart can show correlated firing, and these correlations between pairs of cells are often stronger when they are stimulated by a single contour. This suggests that the correlations reflect not only permanent connections between cells with similar receptive fields, but in addition may encode information that the activating stimuli are continuous or part of a single object. I also find that, as in the cat, and contrary to some other reports on experiments in monkeys, the correlated firing is often rhythmic. These recordings further indicate that periods of rhythmicity are associated with stronger interneuronal synchrony, which is consistent with the hypothesis that recurrent feedback loops are involved in generating both. 3. Pairs of cells in the same cortical column, but at different depths also showed correlated firing, but with several milliseconds difference in timing between layers. This was true for cells at different depths within layer 2/3 and for pairs of cells in different layers (2/3 vs. 4B or 4C alpha), providing evidence for cross-talk between the magno- and parvocellular streams.
8793759
Neuronal synchrony in relation to burst discharge in epileptic human temporal lobes.
1. Synchronous interactions between neurons in mesial temporal structures of patients plex partial seizures were studied using cross-correlation analyses. We recorded spontaneous activity from 293 neurons in 24 patients during the interictal state. Patients had depth microelectrodes chronically implanted in amygdala, hippocampal formation, and parahippocampal gyrus to record epileptic activity. One hundred twenty-five cells were recorded from the temporal monly initiating seizures (ipsilateral temporal lobe), and 168 cells from the contralateral temporal lobe. Eight hundred forty-three cross-correlograms were constructed between all pairs of simultaneously recorded neurons. Cross-correlogram peaks or troughs that exceeded confidence limits within 200 ms of the origin were considered evidence of synchronous neuronal interaction. 2. Synchronous neuronal interactions were observed in 223 of 843 cross-correlograms. Eighty-six percent of these 223 cross-correlograms showed significant central peaks (peak interactions), suggesting excitatory interactions, whereas the remainder displayed significant central troughs (trough interactions), suggesting inhibitory interactions. 3. Cross-correlograms constructed using cells from the ipsilateral temporal lobe (ipsilateral cross-correlograms) were more likely to display significant central troughs (14/262) than cross-correlograms constructed using cells from the contralateral temporal lobe (6/376; contralateral cross-correlograms). Similarly, cross-correlograms constructed using one cell from each hemisphere (11/205; bilateral cross-correlograms) were also more likely to display significant central troughs (trough interactions) than contralateral cross-correlograms. Both ipsilateral (77/262) and contralateral cross-correlograms (102/376) were more likely to display significant central peaks (peak interactions) than bilateral cross-correlograms (13/205). 4. Cells from different structures in the ipsilateral temporal lobe were more likely to display significant trough interactions (10/ 114) than neurons in different contralateral structures. We pared the proportion of significant peak interactions between cells within the ipsilateral and contralateral sides of each structure. Neurons in the contralateral entorhinal cortex were more likely to show peak interactions (21/55) than cells from the ipsilateral entorhinal cortex (3/31). Also, cells in the ipsilateral presubiculum showed a higher proportion of peak interactions (9/16) than their contralateral homologues (5/30). 5. Neuronal burst discharges were defined as three or more action potentials (or spikes) separated by interspike intervals of < or = 30 ms, or two spikes separated by an interval of < or = 15 ms. The contribution of burst discharge to synchronous peak interaction pared between temporal lobes. Cells used to construct ipsilateral cross-correlograms displaying significant central peaks (n = 154) were found to have significantly reduced burst discharge contributions to the observed synchronous peaks parison with their contralateral homologues (n = 204). When cross-correlograms were separated by regions, burst discharge contributions to synchronous peak interactions between cells in the ipsilateral hippocampus (n = 72) were significantly smaller than the contributions from cells in the contralateral hippocampus (n = 44). 6. The results suggest that in the interictal state, synchronous neuronal burst discharge is not a distinguishing feature of epileptogenic regions of patients plex partial seizures, but inhibitory neuronal interactions are increased in regions of seizure initiation. Increases in the strength and spread of local inhibition in seizure initiating regions in these patients may result in a greater proportion of inhibitory interactions and could also cause increased synchrony between isolated action potentials.(ABSTRACT TRUNCATED)
8793758
Microstimulation of primate motor thalamus: somatotopic organization and differential distribution of evoked motor responses among subnuclei.
1. The functional organization of motor responses to microstimulation throughout the primate "motor" thalamus including nucleus ventralis lateralis, pars oralis (VLo); nucleus ventralis posterior lateralis, pars oralis (VPLo); nucleus ventralis lateralis, pars caudalis (VLc); and portions of ventralis anterior (VA) and area X, was systematically studied in awake monkeys. A total of 2,021 sites were examined for their response to microstimulation. Of these, 1,123 were histologically verified as to their location within the motor thalamus. At or near each site, isolated neurons were examined for their responses to somatosensory examination and active movement (n = 1,272). This study was carried out as part of a larger study examining the responses of neurons in the motor thalamus to somatosensory examination, torque-induced limb perturbations, and active movement in a visuomotor step-tracking task. 2. Microstimulation at < or = 40 microA evoked movements in the contralateral limbs, trunk, or face. Evoked movements of the limb were generally maximal about a single joint. 3. There was a differential response to microstimulation between subnuclei of the motor thalamus. In order of decreasing frequency, the percentages of sites within each subnucleus from which movements were evoked were as follows: VPLo, 93% (449 of 483); VLo, 21% (57 of 272); VLc, 11% (15 of 140); VA, 1% (1 of 85); and reticular nucleus, 0% (0 of 65). In VPLc, 44% (34 of 78) of sites examined were microexcitable. However, these were almost all within 500 microns of the border of VPLo, suggesting they may have occurred as a result of current spread to adjacent VPLo. Although area X was not sampled in its entirety, it did not appear to be microexcitable. 4. Microexcitable responses had a somatotopic organization, similar to that for neuronal responses to sensorimotor examination, with leg responses found most laterally and arm and face responses found progressively more medially. 5. Zones in VPLo generally ranging from 500 to 1,500 microns were found in which microstimulation resulted in the same motor response. These microexcitable zones resemble those described for the striatum and were termed thalamic microexcitable zones (TMZ). TMZs also resemble cortical efferent zones in that both are somatotopically organized, may affect a single muscle or group of muscles, have low thresholds for microstimulation with sharp boundaries that lie adjacent to other microexcitable zones with the opposite effects, and are of approximately the same dimension. 6. This study suggest that a fundamental unit of motor organization, i.e., single muscle or joint, is preserved at the thalamic level in the form of TMZs, and that these fundamental units of organization may contribute to the modular organization of the cortex.
8793760
Contractile properties of single motor units in human toe extensors assessed by intraneural motor axon stimulation.
1. Single motor axons innervating human toe extensor muscles were selectively stimulated through a tungsten microelectrode inserted percutaneously into the peroneal nerve. Twitch and tetanic forces were measured from a strain gauge over the proximal phalanx of the toe generating the greatest force. Twitch data were obtained from 19 single motor units in nine subjects: 8 motor units supplied extensor hallucis longus (EHL), 5 motor units supplied extensor digitorum longus (EDL), and 6 motor units supplied extensor digitorum brevis (EDB). Unpotentiated twitch forces ranged from 6.3 to 78.1 mN (20.0 +/- 4.0 mN, mean +/- SE), with the distribution highly skewed toward small forces. Twitch contraction and half-relaxation times were 74.8 +/- 3.9 and 78.6 +/- 6.0 ms, respectively. Compared with motor units in human thenar muscles, those in human toe extensor muscles were stronger but slower. However, as in thenar motor units, twitch force and contraction time were not related. 2. Force-frequency relationships were determined for 13 units (5 EDL, 5 EHL, 3 EDB) by stimulating each unit with short trains (1.0-5.0 s) of constant frequency (2-100 Hz). Peak force was related to stimulus frequency in a sigmoid fashion. The steep region of the curve extended from 5.5 +/- 0.7 (SE) Hz to 16.3 +/- 1.1 Hz for all units, and the stimulus frequency required to generate half-maximal force (9.6 +/- 0.6 Hz) was close to the center of the steep range. This frequency, which was inversely related to twitch contraction time, was lower than the frequency required to develop half-maximal force of human thenar motor units (12 +/- 4 Hz, mean +/- SD). The slopes of the regression lines relating force to puted over the steep range for each unit, were also lower for the toe extensors (3.7 +/- 0.7 mN/Hz) than for the thenar muscles (6 +/- 1 mN/Hz). 3. Maximal tetanic forces ranged from 29.9 to 188.1 mN (89.0 +/- 16.5 mN, mean +/- SE), and were generated at stimulus frequencies from 15 to 100 Hz (median 50 Hz). The stimulation frequency required for fused tetani (absence of noticeable force fluctuation) was generally less than that required for maximum tetanic force. The mean twitch-tetanus ratio, calculated for unpotentiated twitches, was 0.22 +/- 0.02 (range 0.15-0.41). This ratio was higher than for human thenar motor units (0.14 +/- 0.06, mean +/- SE). After twitch potentiation of 10 units, the mean twitch-tetanus ratio increased to 0.28 +/- 0.04. 4. The effects of preceding each stimulus train with a short interstimulus interval (10 ms) on force production at each frequency were examined in nine motor units. Peak forces at the onset of each contraction were higher when such an "initial doublet" preceded stimulus trains of < or = 20 Hz, but the mean force at the end of each stimulus train was not significantly affected at any frequency. 5. Eight units were stimulated with a train that increased in frequency continuously from 2 to 80 Hz, and then decreased symmetrically. This pattern resulted in peak forces that were higher on the descending limb of the stimulus train, the force-frequency relationship tracing a hysteresis loop. Hysteresis was exhibited because damping in the neuromuscular system causes the mechanical output of muscle to lag behind neural input. Thus, in non-steady-state conditions (as in most forms of natural activity), somewhat higher firing rates may be required to attain a particular level of force; once attained, force output will be transiently unresponsive to diminution of firing rate. 6. We conclude that there are differences in the contractile properties of single motor units in human toe extensor muscles (involved in posture and otion) and thenar muscles (involved in prehension and manipulation). Twitch-tetanus ratios were greater for motor units in the toe extensors, and this property accounted for the lower force sensitivity of these units to increases in frequency. (ABSTRACT TRUNCATED)
8793761
Interaction of smooth pursuit and the vestibuloocular reflex in three dimensions.
1. What is the neural mechanism of vestibuloocular reflex (VOR) cancellation when a subject fixates a target moving with the head? One theory is that the moving target evokes pursuit eye movements that add to and cancel the VOR. A recent finding with implications for this theory is that eye velocity vectors of both pursuit and the VOR vary with eye position, but in different ways, because pursuit follows Listing's law whereas the VOR obeys a "half-Listing" strategy. As a result, pursuit cannot exactly cancel the VOR in most eye positions, and so the pursuit superposition theory predicts an eye-position-dependent pattern of residual eye velocities during cancellation. To test these predictions, we measured eye velocity vectors in humans during VOR, pursuit, and cancellation in response to torsional, vertical, and horizontal stimuli with the eyes in different positions. 2. For example, if a subject is rolling clockwise (CW, frequency 0.3 Hz, maximum speed 37.5 deg/s) while looking 20 deg up, the VOR generates an eye velocity that is mainly counterclockwise (CCW), but also leftward. If we then turn on a small target light, located 20 deg up and moving with the subject, then pursuit superposition predicts that the ponent of eye velocity will shrink and the ponent will reverse, from leftward to rightward. This pattern was seen in all subjects. 3. Velocities depended on eye position in the predicted way; e.g., when subjects looked 20 deg down, instead of 20 deg up, during CW roll, the reversal of horizontal eye velocity went the other way, from rightward to leftward. And when gaze was 20 deg right or left, analogous reversals occurred in the vertical eye velocity, again as predicted. 4. Analogous predictions for horizontal and vertical stimulation were also borne out by the data. For example, when subjects rotated rightward while looking 20 deg up, the VOR response was leftward and CCW. When the target light switched on, the ponent of the response reversed, ing CW. And analogous predictions for other eye positions and for vertical stimulation also held. 5. For all axes of stimulation and all eye positions, eye velocity during cancellation was roughly parallel with the gaze line. This alignment is predicted by pursuit superposition and has the effect of reducing retinal image slip over the fovea. 6. The fact that plex dependence of eye velocity on the stimulation axis and eye position predicted by pursuit superposition was seen in all subjects and conditions suggests strongly that the VOR indeed is canceled additively by pursuit. However, eye velocities during cancellation were consistently smaller than predicted. This shrinkage indicates that a second mechanism, besides pursuit superposition, attenuates eye velocities during cancellation. The results can be explained if VOR gain is reduced by approximately 30%, and if, in addition, pursuit is driven by retinal slip rather than reconstructed target velocity in space.
8793762
Accuracy of motor responses in subjects with and without control of antagonist muscle.
1. The aim of this study was to investigate the role of the antagonist muscle in determining the accuracy of fast, single-joint motor responses to a target. We recently found that C5/C6 tetraplegic subjects, who lacked voluntary control of their triceps muscle, were less accurate than control subjects in producing fast flexion movements to a target. 2. Two hypotheses are proposed to account for these larger errors: 1) the ability of tetraplegic subjects pensate for errors arising early in the motor response is impaired because of the lack of antagonist muscle activation; or 2) tetraplegic subjects lack antagonist (braking) force, so they must use much smaller accelerative forces when they move, in order to avoid overshooting their target. Because studies have shown that low levels of force are produced with less relative accuracy than larger forces, this relative inaccuracy of force generation by the motor control system at low force levels is responsible for the inaccuracy of tetraplegics' movements. To test these two hypotheses, pared the variability of "fast and accurate as possible" force pulses in four control subjects and four C5/C6 tetraplegic subjects to targets at 15, 30, and 45% of maximum voluntary contraction. Multiple regression analyses were performed to look for patterns of agonist or antagonist muscle activation consistent pensatory adjustments for early trajectory errors in both groups of subjects. 3. Force rise time was significantly prolonged in tetraplegic subjects, although there was some overlap between groups. At similar levels of effort, there were no significant differences in constant and variable errors of control and tetraplegic subjects. We also found no consistent statistical evidence for the presence pensatory electromyographic activity in either group of subjects. Subjects who lacked the ability to make corrections involving the triceps muscle performed as well as subjects with normal triceps strength. This suggests that a corrective mechanism involving the triceps must have a weak role, if any, in these experiments. 4. Together with our observation that lower force targets are indeed associated with larger relative variable errors, in both control and tetraplegic subjects, the above results lead us to conclude that the second hypothesis listed above is more likely correct. The antagonist muscle clearly enables the production of briefer force pulses. In addition, the antagonist indirectly contributes to the accuracy of isotonic movements because antagonist braking allows larger agonist forces to be used. These larger agonist forces are less variable, and produce more accurate movements, than the smaller forces used by tetraplegic subjects.
8793763
Synaptic plasticity of the interpositorubral pathway functionally related to forelimb flexion movements.
1. Some connections from the afferents to the magnocellular red nucleus (RNm), like the corticorubral synapses, have plastic properties that are thought to contribute to long-term changes such as functional readaptation, motor learning, and the establishment of conditioned responses. Because previous studies have focused on corticorubral synaptic reorganization after these events, we attempted to investigate cerebellorubral connections in intact adult cats during associative conditioning by pairing electrical stimulation of interpositus nucleus [the conditional stimulus (CS)] with electrical simulation of the forelimb [the unconditional stimulus (UCS)]. A large increase in the amplitude of the forelimb flexion (conditioned response) induced by the CS was observed after several days of paired CS-UCS presentations. 2. For this purpose, both behavioral and electrophysiological methods were used to correlate synaptic plasticity with changes in the motor responses. The somatotopically organized sensorimotor network functionally related to the control of the elbow joint movements was studied in awake adult cats. This circuit was defined on the basis of sites at which elbow flexions could be evoked both as a CS and a UCS. The CS was applied in the cerebellar interpositus nucleus (IN) site and the UCS was given to the skin on the dorsum of the distal part of the forepaw. Daily classical conditioning consisted of repetitive pairings of CS and UCS with an interstimulus interval (ISI) of 100 ms. 3. The transmission efficacy resulting from the conditioning was tested in various targets of the cerebellar efferent pathway, including the RNm. Electrophysiological responses evoked in these relay structures by the CS and the forelimb angular deviations were simultaneously recorded throughout each daily conditioning session. The surface areas of the rubral responses to CS and the percentage response rate, the angular deviation (amplitude), and the latency of the motor responses were systematically measured throughout the conditioning procedure. Test sessions were also performed before and after each period of conditioning. Quantification and statistical analysis were carried out to determine whether changes observed in interpositorubral synaptic transmission and in the motor responses evoked by the CS were correlated. 4. Daily repetition of paired CS and UCS according to a predefined and fixed temporal schedule led to an increase in the response rate and amplitude of the forelimb flexions. A procedure with repeated presentation of CS preceded by UCS was used to produce extinction of the enhanced motor responses. The associative nature of these changes was confirmed by the fact that the CS given alone for 11 days in a control condition failed to produce any modification of the motor response. 5. The changes in the flexion movements were panied by a nearly parallel increase of the amplitude of the "postsynaptic field potentials" evoked in the RNm by the CS (IN stimulation). Changes in the transmission efficacy of the interpositorubral synapses stayed stable even after several days of interruption and remained constant up the extinction period. Changes affecting both the motor and the central responses were significantly correlated, suggesting that modifications in the interpositorubral transmission efficacy might be one of the plastic correlates of forelimb flexion conditioning. 6. Examination of the neuronal excitability within either the IN or the RNm or in the spinal cord failed to show any evidence of facilitation suggesting that the increases in the postsynaptic rubral field potential were attributable to a plasticity of the interpositorubral connections. The long-lasting duration of the increase of cerebellorubral synaptic transmission suggests that structural changes were induced by conditioning in the intact animal. (ABSTRACT TRUNCATED)
8793764
Activity of neurons in monkey superior colliculus during interrupted saccades.
1. Recent studies of the monkey superior colliculus (SC) have identified several types of cells in the intermediate layers (including burst, buildup, and fixation neurons) and the sequence of changes in their activity during the generation of saccadic eye movements. On the basis of these observations, several hypotheses about the organization of the SC leading to saccade generation have placed the SC in a feedback loop controlling the amplitude and direction of the impending saccade. We tested these hypotheses about the organization of the SC by perturbing the system while recording the activity of neurons within the SC. 2. We applied a brief high-frequency train of electrical stimulation among the fixation cells in the rostral pole of the SC. This momentarily interrupted the saccade in midflight: after the initial eye acceleration, the eye velocity decreased (frequently to 0) and then again accelerated. Despite the break in the saccade, these interrupted saccades were of about the same amplitude as normal saccades. The postinterruption saccades were usually initiated immediately after the termination of stimulation and occurred regardless of whether the saccade target was visible or not. The velocity-amplitude relationship of the ponent of the saccade fell slightly above the main sequence for control saccades of that amplitude, whereas postinterruption saccades fell near the main sequence. 3. Collicular burst neurons are silent during fixation and discharge a robust burst of action potentials for saccades to a restricted region of the visual field that define a closed movement field. During the stimulation-induced saccadic interruption, these burst neurons all showed a pause in their high-frequency discharge. During an interrupted saccade to a visual target, the typical saccade-related burst was broken into two parts: the first part of the burst began before the initial preinterruption saccade; the second burst began before the postinterruption saccade. 4. We quantified three aspects of the resumption of activity of burst neurons following saccade interruption: 1) the total number of spikes in the pre- and postinterruption bursts, was very similar to the total number of spikes in the control saccade burst; 2) the increase in total duration of the burst (preinterruption period + interruption + postinterruption period) was highly correlated with the increase in total saccade duration (preinterruption saccade + interruption + postinterruption saccade); and 3) the time course of the postinterruption saccade and the resumed cell discharge both followed the same monotonic trajectory as the control saccade in most cells. 5. The same population of burst neurons was active for both the preinterruption and the postinterruption saccades, provided that the stimulation was brief enough to allow the postinterruption saccade to occur immediately. If the postinterruption saccade was delayed by > 100 ms, then burst neurons at a new and more rostral locus related to such smaller saccades became active in association with the smaller remaining saccade. We interpret this shift in active locations within the SC as a termination of the initial saccadic mand and the triggering of a new one. 6. Buildup neurons usually had two aspects to their discharge: a high-frequency burst for saccades of the optimal amplitude and direction (similar to burst neurons), and a low-frequency discharge for saccades of optimal direction whose amplitudes were equal to or greater than the optimal (different from burst neurons). The stimulation-induced interruption in saccade trajectory differentially affected these ponents of buildup neuron discharge. The high-frequency ponent was affected in a manner very similar to the burst neurons.(ABSTRACT TRUNCATED)
8793765
Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. I. Locations of antidromically identified axons in the cervical cord and diencephalon.
1. A goal of this study was to determine the sites in the diencephalon to which neurons in sacral spinal segments of rats project. Therefore, 95 neurons were recorded extracellularly in spinal segments L6-S2 of rats that were anesthetized with urethan. These neurons were activated initially antidromically with currents < or = 30 microA from a monopolar stimulating electrode placed into the contralateral posterior diencephalon. The mean +/- SE current for antidromic activation from these sites was 16 +/- 0.8 microA. These neurons were recorded in the superficial dorsal horn (4%), deep dorsal horn (89%), and intermediate zone and ventral horn (4%). 2. Systematic antidromic mapping techniques were used to map the axonal projections of 41 of these neurons within the diencephalon. Thirty-three neurons (80%) could be activated antidromically with currents < or = 30 microA only from points in the contralateral thalamus and are referred to as spinothalamic tract (STT) neurons. Eight neurons (20%) were activated antidromically with low currents from points in both the contralateral thalamus and hypothalamus, and these neurons are referred to as spinothalamic tract/ spinohypothalamic tract (STT/SHT) neurons. Three additional neurons were activated antidromically with currents < or = 30 microA only from points within the contralateral hypothalamus and are referred to as spinohypothalamic tract (SHT) neurons. The diencephalic projections of another 51 neurons were mapped pletely. These neurons are referred to as spinothalamic/unknown (STT/ U) neurons to indicate that it was not known whether their axons ascended beyond the site in the thalamus from which they initially were activated antidromically. 3. For 31 STT neurons, the most anterior point at which antidromic activation was achieved with currents < or = 30 microA was determined. Fourteen (45%) were activated antidromically only from sites posterior to the plex (VbC) of the thalamus. Sixteen STT neurons (52%) were activated antidromically with low currents from sites at the level of the VbC, but not from more anterior levels. One STT neuron (3%) was activated antidromically from the anteroventral nucleus of the thalamus. 4. STT/SHT neurons were antidromically activated with currents < or = 30 microA from the medial lemniscus (ML), anterior pretectal nucleus (APt), posterior nuclear group and medial geniculate nucleus (Po/MG), and zona incerta in the thalamus and from the optic tract (OT), supraoptic decussation, or lateral area of the hypothalamus. No differences in the sites in the thalamus from which STT and STT/SHT neurons were activated antidromically were apparent. Five STT/SHT neurons (62%) were activated antidromically from points in the thalamus in the posterior diencephalon and from points in the hypothalamus at more anterior levels. Three STT/SHT neurons (38%) were activated antidromically with currents < or = 30 microA from sites in both the thalamus and hypothalamus at the same anterior-posterior level of the diencephalon. All three of these STT/SHT neurons projected to the intralaminar nuclei (parafascicular or central lateral nuclei) of the thalamus. 5. Seven STT/SHT neurons were tested for additional projections to the ipsilateral brain. Two (29%) were activated antidromically with currents < or = 30 microA and at longer latencies from sites in the ipsilateral diencephalon. One could only be activated antidromically from the hypothalamus ipsilaterally. The other was activated antidromically at progressively increasing latencies from points in the ipsilateral brain that extended as far posteriorly as the posterior pole of the MG. 6. Fifty-eight STT, STT/SHT, and STT/U neurons were classified as low-threshold (LT), wide dynamic range (WDR), or highthreshold (HT) neurons based on their responsiveness to innocuous and noxious mechanical stimuli applied to their cutaneous receptive fields.(ABSTRACT TRUNCATED)
8793766
Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. II. Responses to cutaneous and visceral stimuli.
1. A goal of this study was to determine whether neurons in the sacral spinal cord that project to the diencephalon are involved in the processing and transmission of sensory information that arises in the perineum and pelvis. Therefore, 58 neurons in segments L6-S2 were activated antidromically with currents < or = 30 microA from points in the contralateral diencephalon in rats that were anesthetized with urethan. 2. Responses to mechanical stimuli applied to the cutaneous receptive fields of these neurons were used to classify them as low-threshold (LT), wide dynamic range (WDR) or high-threshold (HT) neurons. Twenty-two neurons (38%) responded preferentially to brushing (LT neurons). Eighteen neurons (31%) responded to brushing but responded with higher firing frequencies to noxious mechanical stimuli (WDR neurons). Eighteen neurons (31%) responded only to noxious intensities of mechanical stimulation (HT neurons). LT neurons were recorded predominantly in nucleus proprius of the dorsal horn. Nociceptive neurons (WDR and HT) were recorded throughout the dorsal horn. 3. Cutaneous receptive fields were mapped for 56 neurons. Forty-five (80%) had receptive fields that included at least two of the following regions ipsilaterally: the rump, perineum, or tail. Eleven neurons (20%) had receptive fields that were restricted to one of these areas or to the ipsilateral hind limb. Thirty-eight neurons (68%) had cutaneous receptive fields that also included regions of the contralateral tail or perineum. On the perineum, receptive fields usually passed perianal and perivaginal areas including the clitoral sheath. There were no statistically significant differences in the locations or sizes of receptive fields for LT pared with nociceptive (WDR and HT) neurons. 4. Thirty-seven LT, WDR, and HT neurons were tested for their responsiveness to heat stimuli. Five (14%) responded to increasing intensities of heat with graded increases in their firing frequencies. Thirty-two LT, WDR, and HT neurons also were tested with cold stimuli. None responded with graded increases in their firing frequencies to increasingly colder stimuli. There were no statistically significant differences among the responses of LT, WDR, and HT neurons to either heat or cold stimuli. 5. Forty LT, WDR, and HT neurons were tested for their responsiveness to visceral stimuli by distending a balloon placed into the rectum and colon with a series of increasing pressures. Seventeen (43%) exhibited graded increases in their firing frequencies in response to increasing pressures of colorectal distention (CrD). None of the responsive neurons responded reproducibly to CrD at an intensity of 20 mmHg, and all responded at intensities of > or = 80 mmHg. More than 90% responded abruptly at stimulus onset, responded continuously throughout the stimulus period, and stopped responding immediately after termination of the stimulus. 6. Thirty-one neurons were tested for their responsiveness to distention of a balloon placed inside the vagina. Eleven (35%) exhibited graded increases in their firing frequencies in response to increasing pressures of vaginal distention (VaD). The thresholds and temporal profiles of the responses to VaD were similar to those for CrD. Twenty-nine neurons were tested with both CrD and VaD. Thirteen (45%) were excited by both stimuli, four (14%) responded to CrD but not VaD, and one (3%) was excited by VaD but not CrD. Neurons excited by CrD, VaD, or both were recorded throughout the dorsal horn. 7. As a population, WDR neurons, but not LT or HT neurons, encoded increasing pressures of CrD and VaD with graded increases in their firing frequencies. The responses of WDR neurons to CrD differed significantly from those of either LT or HT neurons. Regression analyses of the stimulus-response functions of responsive WDR neurons to CrD and VaD were described by power functions with exponents of 1.6 and 2.4, respectively.(ABSTRACT TRUNCATED)
8793767
Characterization of six voltage-gated K+ currents in adult rat sensory neurons.
1. Previously three voltage-gated K+ currents were described in neurons from mammalian sensory ganglia: two transient and one sustained. Because there is considerable variability in the gating properties of these three currents, we have investigated the possibility that this variability reflects the presence of additional currents in sensory neurons. 2. Using whole cell patch-clamp techniques, we provide evidence for the existence of six voltage-gated K+ currents in cultured dorsal root ganglion (DRG) neurons from the adult rat. The six currents were identified on the basis of distinct biophysical and pharmacological properties; three currents are transient (IAf, IAht, and IAs), and three are sustained (IKi, IKlt, and IKn). 3. In addition to possessing distinct biophysical and pharmacological properties, four of the six currents are differentially expressed among subpopulations of DRG neurons. IAht is selectively expressed in small-diameter neurons. IKi is expressed more frequently in neurons with an action-potential shoulder, and both IAht and IAs are selectively coexpressed in neurons that respond to the algogenic agent capsaicin. IAf is selectively expressed in large-diameter neurons and is the only current expressed more frequently in neurons without an action-potential shoulder. 4. It is likely that much of apparent variability in the properties of the three voltage-gated K+ currents reported previously in vertebrate sensory neurons can be accounted for by the existence of at least three additional voltage-gated K+ currents described in this report.
8793769
alpha-subunit of CaM-KII increases glycine currents in acutely isolated rat spinal neurons.
1. Here we report that in acutely isolated rat spinal dorsal horn neurons, the glycine receptor can be regulated by exogenous calcium/ calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced glycine receptor-activated current recorded with the use of the whole cell patch-clamp technique. This result suggests that the function of glycine receptor is modulated by CaM-KII, but the cellular mechanism underlying the enhancement of glycine receptor-activated current is still unknown.
8793768
Selective activity of a proctolin analogue reveals the existence of two receptor subtypes.
1. The neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) both potentiates neurally evoked contractions and causes contractures of insect skeletal muscle. In the hindleg extensor tibiae muscle of the locust, Schistocerca gregaria, the proctolin analogue [Afb (p-NO2)2]-proctolin is also able to potentiate neurally evoked contractions but is approximately 1,000-fold less effective in evoking contractures. 2. Proctolin and [Afb (p-NO2)2]-proctolin are equipotent in their ability to elevate the second-messenger inositol trisphosphate in isolated extensor tibiae muscle fiber membranes. 3. [Afb (p-NO2)2]-proctolin is approximately 1,000-fold less effective than proctolin in reducing the resting potassium conductance (GK) in extensor tibiae fibers. 4. We conclude that the action of proctolin on the extensor tibiae muscle is mediated by at least two receptor subtypes and that [Afb (p-NO2)2]-proctolin acts selectively on the receptor that potentiates neurally evoked contractions.
8793770
Role of chloride-homeostasis in the inhibitory control of neuronal network oscillators.
1. Spontaneous synaptic activity in networks formed by dissociated neurons from embryonic rat midbrain was analyzed in tight seal whole cell recordings. 2. Application of furosemide (0.5 mM) to the cell and its surrounding area increased the frequency of spontaneous synaptic currents. Incubation of the culture with furosemide resulted in "rhythmic" burst activity. 3. Furosemide (0.1-0.5 mM) changed equilibrium potentials of inhibitory postsynaptic currents, gamma-aminobutyric acid-A (GABAA) or glycine receptor-mediated Cl- currents by a blockade of Cl(-)-outward transport. Furosemide did not alter the slope conductance of GABAA receptor-mediated currents. Membrane conductance and cell excitability were also unaffected. 4. We conclude that furosemide locked the activity of the network in "burst activity" mode through impairment of inhibition resulting from the disturbance of Cl- homeostasis.
8793771
Monosynaptic activation of medium-lead burst neurons from the superior colliculus in the alert cat.
1. Extracellular recordings were made from medium-lead burst neurons (MLBNs) in the paramedian pontomedullary reticular formation rostral and caudal to the abducens nucleus in the alert cat. 2. Single-pulse stimulation of the contralateral superior colliculus during intersaccadic intervals evoked no response in most MLBNs. When collicular stimulation was applied at the beginning of saccades, spikes of MLBNs were consistently evoked with short latencies. The shortest latency was 0.8 ms, indicating monosynaptic activation of MLBNs from the superior colliculus. 3. Results suggest that monosynaptic excitatory effects from the colliculus are concealed by inhibitory input from omnipause neurons (OPNs) during intersaccadic intervals and that the monosynaptic collicular activation is disclosed when this inhibition is removed by a pause in OPN activity at the beginning of saccades.
8793772
Anterior parietal cortical response to tactile and skin-heating stimuli applied to the same skin site.
1. The response of anterior parietal cortex to skin stimuli was evaluated with optical intrinsic signal imaging and extracellular microelectrode recording methods in anesthetized squirrel monkeys. 2. Nonnoxious mechanical stimulation (vibrotactile or skin tapping) of the contralateral radial interdigital pad was panied by a decrease in reflectance (at 833 nm) in sectors of cytoarchitectonic areas 3b and 1. This intrinsic signal was in register with regions shown by previous receptive field mapping studies to receive low-threshold mechanoreceptor input from the radial interdigital pad. 3. A skin-heating stimulus applied to the contralateral radial interdigital pad with a stationary probe/thermode evoked no discernable intrinsic signal in areas 3b and 1, but evoked a signal within a circumscribed part of area 3a. The region of area 3a responsive to skin heating with the stationary probe/thermode was adjacent to the areas 3b and 1 regions that developed an intrinsic signal in response to vibrotactile stimulation of the same skin site. Skin heating with a stationary probe/thermode also evoked intrinsic signal in regions of areas 4 and 2 neighboring the area 3b/1 regions activated by vibrotactile stimulation of the contralateral radial interdigital pad. 4. The intrinsic signal evoked in area 3a by a series of heating stimuli to the contralateral radial interdigital pad (applied with a stationary probe/thermode) increased progressively in magnitude with repeated stimulation (exhibited slow temporal summation) and remained above prestimulus levels for a prolonged period after termination of repetitive stimulation. 5. Brief mechanical stimuli ("taps") applied to the contralateral radial interdigital pad with a probe/thermode maintained either at 37 degrees C or at 52 degrees C were panied by the development of an intrinsic signal in both area 3a and areas 3b/1. For the 52 degrees C stimulus, the area 3a intrinsic signal was larger and the intrinsic signal in areas 3b/1 smaller than the corresponding signals evoked by the 37 degrees C stimulus. 6. Spike discharge activity was recorded from area 3a neurons during a repetitive heating stimulus applied with a stationary probe/ thermode to the contralateral radial interdigital pad. Like the area 3a intrinsic signal elicited by repetitive heating of the same skin site, the area 3a neuron spike discharge activity also exhibited slow temporal summation and poststimulus response persistence. 7. The experimental findings suggest 1) a leading role for area 3a in the anterior parietal cortical processing of skin-heating stimuli, and 2) the presence of inhibitory interactions between the anterior parietal responses to painful and vibrotactile stimuli consistent with those demonstrated in recent cortical imaging and psychophysical studies of human subjects.
8793773
Posterior pedicular screw instrumentation and anterior interbody fusion in adult lumbar spondylolysis or grade I spondylolisthesis with segmental instability.
Between 1988 and 1993, we treated 21 adults with symptomatic lumbar spondylolysis by bined surgery of posterior stabilization and anterior interbody fusion. Our indication for bined surgery was persistent pain that was unresponsive to conservative measures and segmental instability on flexion-extension roentgenogram. The patients' mean age at the time of surgery was 34 years (range 24-42 years). All patients showed degenerated disks on preoperative magnetic resonance imaging. The mean follow-up period was 30.4 months. The clinical result was excellent or good in 95%, and the radiographic fusion was successful in 95%. Prolonged pain at the donor site was the plication, which usually disappeared by 3 months after the operation. We mend bined surgery of posterior instrumentation and anterior fusion to stabilize symptomatic adult lumbar spondylolysis.
8793774
Flexion-distraction injury of the lumbar spine: influence of load, loading rate, and vertebral mineral content.
The biomechanical response of the lumbar spine bined flexion-shear loading was determined experimentally. The injury model simulated flexion-distraction trauma to the lumbar spine. Forty-eight lumbar functional spinal units (FSUs) were subjected to dynamic loading to injury with six different load types. The reactive forces and moments and resulting deformity were determined. Static physiologic loading was performed before and after the injurious loading to assess residual injury. The biomechanical response of FSUs was dependent on the amount of load and loading rate. The vertebral bone mineral content explained most of the biologic variation of the results. An osteoporotic or severely degenerated spine will be more easily rendered unstable after trauma with lower deformity. Injury at high loading rates will create instability with lower deformity. In vitro experiments should be performed on entire spinal units and bined loads.
8793775
Effects of OP-1206 (prostaglandin E1) on nerve-conduction velocity in the dog cauda equina subjected to acute experimental compression.
The effect of OP-1206, a prostaglandin E1 derivative, on cauda equina function was analyzed in a model for acute cauda pression in the dog. An inflatable balloon was placed under the lamina of the seventh lumbar vertebra in the dog and muscle action potential area (MAP area) and nerve-conduction velocity (NCV) were monitored during 2 h pression and 1.5 h of recovery. OP-1206 was infused systemically at three concentrations. Only the highest concentration (30 ng/kg/min) of OP-1206 could prevent the reduction in NCV. However, this concentration had no similar effect on the MAP area. The data suggest the potential therapeutic use of prostaglandin E1 analogues for the future treatment of intermittent claudication.
8793776
The effect of postlaminectomy spinal instability on the outcome of lumbar spinal stenosis patients.
Between 1986 and 1990, 37 of 72 patients undergoing pressive lumbar laminectomy with medial facetectomy for lumbar stenosis at The Ohio State University were seen in follow-up at a mean of 31 months (range, 14-63 months) after their laminectomy and were evaluated by questionnaire, detailed neurologic examination, and static and dynamic lumbar radiographs. Thirteen patients who had undergone fusion or who had extenuating medical circumstances were excluded, leaving 24 patients for whom laminectomy was the sole treatment for lumbar stenosis. Postoperatively, normal walking improved from 4 to 45% of patients, sensory deficits decreased from 63 to 25%, and ability to perform most or all desired activities increased from 25 to 70%. Urinary function was unchanged. Thirteen patients (54%) showed radiographic signs of instability. All patients who were declared radiographically stable could walk without a prosthetic aid or normally; 62% of the unstable patients required aid for walking. All of the patients with a poor ambulatory e were radiographically unstable. Compared with stable patients, unstable patients had a significant (p < 0.01) decrease in their ambulatory ability. There was a clear correlation between the degree of listhesis and postoperative ambulatory status (p < 0.01). The unstable patients with a poor ambulatory e followed one of three clinical courses: improvement with later deterioration, improvement with a plateau at a poor functional level, or failure to improve from a poor functional level. In conclusion, (a) although instability did not necessarily preclude a good e, a poor ambulatory e was always associated with instability; (b) laminectomy can effectively ameliorate the symptoms of lumbar stenosis; however, there is a subset of patients in whom laminectomy is associated with instability and a poor clinical course.
8793778
Outcome after Wiltse pedicle screw removal.
Thirty-five patients were retrospectively reviewed after hardware removal after previous posterior lumbar spinal fusion by using Wiltse pedicle screw fixation. Pseudarthrosis was intraoperatively confirmed in 10 patients. Thirty of 35 patients were reviewed at an average of 17.5 months (range, 6-57 months). Of 30 patients, 30 had persistent back pain that limited activities and lumbar motion. Patients found to have pseudarthroses were significantly more likely to have less pain, use fewer narcotic medications, and have an improved quality of life after reoperation than patients found to have solid fusions. Postsurgical assessment of fusion is difficult, with instrumentation making exploration the most reliable method determining the state of arthrodesis. Accurate preoperative assessment of the fusion mass is the most important factor in deciding whether or not to reoperate on patients after Wiltse pedicle screw arthrodesis of the lumbar spine.
8793777
Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings.
Twenty-five consecutive patients who had previously undergone lumbar fusion using stainless steel pedicle screw instrumentation plained of persistent, severe pain were identified for prospective study. All patients had been scheduled for hardware removal and fusion inspection. Studies to rule out pseudarthrosis included plain radiography, flexion and extension puted tomography, and bone scintigraphy. Each preoperative radiographic study was then evaluated in a blinded fashion by a single independent radiologist and was determined to show fusion or pseudarthrosis. Each patient then underwent surgery, at which time the pedicle screw instrumentation was removed and the fusion was inspected. Using surgical inspection as absolute evidence of fusion or pseudarthrosis, statistical analysis was undertaken to evaluate the predictive value of the radiographic studies singly and bination. No statistically significant correlation was found.