bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilation with positive end-expiratory airway pressure causes leukocyte retention in human lung
Authors: Loick H. M. , Wendt M. , Rotker J. , Theissen J. L.
Published: December 2017

We examined the effect of assisted ventilation with different positive end-expiratory airway pressures (PEEP) on pulmonary leukocyte retention in humans after cardiopulmonary bypass. Eight patients who underwent heart surgery were ventilated in the postoperative phase briefly with 10 (39.6 +/- 0.9 s) and 20 cmH2O (40.3 +/- 1.0 s) PEEP. Before, during, and after this ventilatory maneuver, blood was withdrawn simultaneously from catheters placed in the pulmonary and radial arteries for blood cell differentials. At the same time points, pulmonary and systemic hemodynamics were recorded. During PEEP ventilation, there was a four- (10 cmH2O PEEP) and an eightfold (20 cmH2O PEEP) increase in mixed venous-arterial leukocyte cell difference compared with baseline. This phenomenon was based mainly on a transpulmonary cell difference of polymorphonuclear cells. Likewise, the lymphocytes were entrapped in the pulmonary vasculature during PEEP ventilation. During the ventilatory maneuver, the pulmonary blood flow was significantly reduced; it was indexed by a declined cardiac output. We conclude that PEEP ventilation in the post-operative phase after cardiopulmonary bypass causes pulmonary polymorphonuclear cell entrapment. The most likely mechanism for this phenomenon is the compression of alveolar capillaries and reduced pulmonary blood flow in response to the raised alveolar pressure.
Sternum dependence of rib displacement during breathing
Authors: De Troyer A. , Wilson T. A.
Published: December 2017

The parasternal intercostals are the primary determinant of the inspiratory cranial displacement of the ribs in the dog. When they contract, however, these muscles also cause a caudal displacement of the sternum, presumably an expiratory motion. The present studies were designed to assess the effects of this sternal displacement on the cranial displacement of the ribs and on lung volume. Twelve supine anesthetized animals were studied. We first measured, in four paralyzed animals, the displacement of the ribs and sternum produced by known external forces applied to the ribs, the sternum, or both simultaneously. From these measurements, the elastic coupling between the ribs and sternum was determined. We then studied, in eight animals, the effect of sternal motion on rib motion and tidal volume during spontaneous breathing. Rib and sternal displacements and tidal volume were measured first with the sternum free to move caudally during inspiration and then with the sternum constrained to prevent caudal motion. Preventing the sternum from moving caudally caused a 24% increase in the inspiratory cranial displacement of the ribs; this increased displacement of the ribs agreed well with the elastic coupling between the sternum and the ribs as determined from the force-displacement observations. Tidal volume, however, remained unchanged. These observations indicate that the caudal displacement of the sternum produced by the parasternal intercostals reduces the cranial displacement of the ribs but probably increases the lateral expansion of the rib cage.
Developmental changes in diaphragm contractile properties
Authors: Moore B. J. , Feldman H. A. , Reid M. B.
Published: December 2017

The contractile properties of pre- and early postnatal respiratory muscles are incompletely understood. We examined the effects of development on isometric contractile properties, with an emphasis on properties at 37 degrees C. One-day-old (n = 10), 3-wk-old (n = 10), and adult (n = 10) rabbits were studied. Isometric contractile properties of costal diaphragm strips were measured in vitro by using direct stimulation. Twitch and maximal, i.e., fused, tetanic force production increased with strip dimension and with age. Maximal tetanic force developed per unit cross-sectional area (stress) was significantly decreased in muscle from 1-day olds, whereas it was greatest in muscle from 3-wk olds. Twitch stress was similar in all three groups. Only when the stimulus duration was prolonged did twitch and fused tetanic force achieve maximal values values for the 1-day-old and 3-wk-old strips, suggesting less effective excitation-contraction coupling in those muscles. We conclude that immature rabbit diaphragm has unique isometric contractile properties and stimulus parameter requirements that cannot be deduced from studies using mature diaphragm.
Inhaled nitric oxide: dose response and the effects of blood in the isolated rat lung
Authors: Rich G. F. , Roos C. M. , Anderson S. M. , Urich D. C. , Daugherty M. O. , Johns R. A.
Published: December 2017

Inhaled nitric oxide (NO) is a vasodilator selective to the pulmonary circulation. Using isolated rat lungs, we determined the dose-response relationship of NO and the role of blood in mediating pulmonary vasodilation and selectivity. Inhaled 20, 50, 100, and 1,000 ppm NO attenuated (P < 0.001) hypoxic pulmonary vasoconstriction by 16.1 +/- 4.9, 22.6 +/- 6.8, 28.4 +/- 3.5, and 69.3 +/- 4.2%, respectively. Inhaled 13, 34, 67, and 670 ppm NO attenuated the increase in pulmonary arterial pressure secondary to angiotensin II more (P < 0.001) in Greenberg-Bohr buffer- (GB) than in blood-perfused lungs (51.7 +/- 9.9, 71.9 +/- 8.9, 78.2 +/- 5.3, and 91.9 +/- 2.1% vs. 14.3 +/- 4.1, 23.8 +/- 4.6, 28.4 +/- 3.8, and 55.5 +/- 5.9%, respectively). Samples from GB- but not blood-perfused lungs contained NO (93.0 +/- 26.3 nM). Intravascular NO attenuated the response to angiotensin II more (P < 0.001) in GB- (with and without plasma) than in blood- (hematocrit = 41 and 5%) perfused lungs (75.6 +/- 6.4 and 70.9 +/- 4.8% vs. 22.2 +/- 2.4 and 39.4 +/- 7.6%). In conclusion, inhaled NO produces reversible dose-dependent pulmonary vasodilation over a large range of concentrations. Inhaled NO enters the circulation, but red blood cells prevent systemic vasodilation and also a significant amount of pulmonary vasodilation.
Measuring intrasubject variability: use of the jacknife in doubly labeled water experiments
Authors: Broemeling L. D. , Wolfe R. R.
Published: December 2017

The doubly labeled water technique measures energy expenditure; however, very little has appeared in the literature regarding estimation of the intrasubject variation. By use of a statistical resampling procedure called the jackknife, the standard deviation of the determination of energy expenditure in each subject is evaluated. Jackknife methods exploit the regression techniques that are already used with the doubly labeled water technique and are very easy to implement. Estimates of sample sizes for future experiments can easily be done with the jackknife. These formulas give the number of determinations of isotopic enrichment of hydrogen and oxygen over time that are needed to achieve a given degree of accuracy in estimating energy expenditure. An example with two human subjects illustrates the methodology of the jackknife.
Morphometry of methacholine-induced bronchoconstriction in the rat
Authors: Eidelman D. H. , Lei M. , Ghezzo R. H.
Published: December 2017

It has been suggested that parenchymal viscoelasticity accounts for a large proportion of resistive pressure losses induced by smooth muscle agonists. We used morphometric methods to evaluate the relative contributions of parenchyma and airways to mechanical changes during methacholine- (MCh) induced bronchoconstriction. We measured tracheal pressure and tidal volume in 17 open-chest mechanically ventilated Sprague-Dawley rats (frequency = 1.5 Hz, tidal volume = 2 ml, positive end-expiratory pressure = 5 cmH2O) after saline (n = 7, C), 16 mg/ml MCh (n = 5, L), and 256 mg/ml MCh (n = 5, H) aerosols. We calculated pulmonary resistance (RL) and elastance (EL) by fitting the equation PL = VRL + VEL + K, where PL is transpulmonary pressure, V is flow, and V is volume. V was obtained numerically from V. Lungs were rapidly frozen in liquid N2 30 s after aerosolization and processed with freeze substitution. Using midsagittal slices of left lung, we measured airway narrowing as the ratio of lumen area (aBM) subtended by the basement membrane perimeter (LBM) to predicted maximal lumen area (ABM = LBM2/4 pi). Air space size was estimated as mean linear intercept (Lm) and parenchymal distortion as standard deviation of linear intercepts (SDi). Lm was increased in L and H animals, reflecting hyperinflation; aBM/ABM in 0.17- to 0.43-mm-diam airways decreased progressively from C to L to H animals, reflecting bronchoconstriction. By use of stepwise multiple linear regression, the contribution of Lm to variance in mechanics was found to consistently exceed or equal that of aBM/ABM. SDi contributed little once Lm was taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)
Correlations between flow resistance and geometry in a model of the human nose
Authors: Schreck S. , Sullivan K. J. , Ho C. M. , Chang H. K.
Published: December 2017

The relationship between the pressure losses within the nasal airways and nasal geometry were studied in a 3:1 scale model. The geometry of the model was based on magnetic resonance images of the skull of a healthy male subject. Pressure measurements, flow visualization, and hot-wire anemometry studies were performed at flow rates that, in vivo, corresponded to flows of between 0.05 and 1.50 l/s. The influence of nasal congestion and the collapse of the external nares were examined by using modeling clay to simulate local constrictions in the cross section. A dimensionless analysis of the pressure losses within three sections of the airway revealed the influence of various anatomic dimensions on nasal resistance. The region of the exterior nose behaves as a contraction-expansion nozzle in which the pressure losses are a function of the smallest cross-sectional area. Losses in the interior nose resemble those associated with channel flow. The nasopharynx is modeled as a sharp bend in a circular duct. Good correspondence was found between the predicted and actual pressure losses in the model under conditions that stimulated local obstructions and congestion.
Assessment of postpreservation rat lung function using a new model for extended venous reperfusion
Authors: DeCampos K. N. , Waddell T. K. , Slutsky A. S. , Post M. , Patterson G. A.
Published: December 2017

Understanding the physiological significance of biochemical events after lung preservation in rats has been hampered by the lack of a suitable model for physiological assessment. We have developed an ex vivo paracorporeal rat lung perfusion model that permits hemodynamic and gas exchange evaluation of lung function. After anesthesia and heparinization, the heart-lung block was removed and the left lung was reperfused for 1 h at a constant flow of 4 ml/min with homologous venous blood drained from the inferior vena cava of the paracorporeal (host) rat. The lung effluent was returned at the same flow rate to the host distal aorta. The model was validated by the assessment of lung function after room temperature ischemia. Animals were allocated into three groups (n = 6) according to the ischemic interval (group 1, 20 min; group 2, 3 h; group 3, 4 h). In groups 1 and 2, PO2, PCO2, mean airway pressure, and pulmonary arterial pressure were within the normal ranges and stable throughout the experiment. In contrast, lungs in group 3 demonstrated higher pulmonary arterial pressure and lower blood effluent PO2 than were found in either group 1 or 2. A significant weight gain during reperfusion was observed only in group 3 (4.23 +/- 0.9 g; P < 0.002). For each lung, the final blood effluent PO2 correlated with the weight gain (R2 = 0.81; P < 0.0001). Our results indicate that this model can be used reliably to detect lung dysfunction after ischemic injury.
Contribution of vasopressin to blood pressure regulation during hypovolemic hypotension in humans
Authors: Hirsch A. T. , Majzoub J. A. , Ren C. J. , Scales K. M. , Creager M. A.
Published: December 2017

In animals subjected to hemorrhage, plasma arginine vasopressin concentrations increase to levels sufficient to cause vasoconstriction, thus attenuating the hypotensive response. The purpose of this study was to examine the contribution of vasopressin to blood pressure regulation during hypotension in humans. Hypotension was induced in twelve normal subjects by lower body negative pressure (LBNP) before and after intravenous administration of vasopressin V1 receptor antagonist. Before drug administration, LBNP reduced systolic blood pressure from 125 +/- 4 to 78 +/- 12 mmHg (P < 0.01) as vasopressin concentration increased from 2.9 +/- 0.6 to 17 +/- 6 pg/ml (P < 0.05). After administration of the vasopressin antagonist, LBNP reduced systolic blood pressure from 128 +/- 3 to 89 +/- 11 mmHg (P < 0.01). The hypotensive response to LBNP was not potentiated by inhibiting vasopressin's vasoconstrictive effects (P = NS). Thus hypotension causes marked increases in plasma vasopressin concentration. In contrast to findings in animal studies, however, vasopressin does not contribute to the maintenance of blood pressure during hypotension in humans.
Assessment of methacholine-induced airway constriction by ultrafast high-resolution computed tomography
Authors: Amirav I. , Kramer S. S. , Grunstein M. M. , Hoffman E. A.
Published: December 2017

Assessment of changes in airway dimensions during bronchoconstriction is conventionally based on measurements of respiratory mechanics. We evaluated the efficacy of ultrafast high-resolution computed tomography (UHRCT) to directly determine the dynamic changes in cross-sectional area (CSA) of airways in response to methacholine (MCh). UHRCT scans were obtained at functional residual capacity before (baseline) and after intravenous bolus injections of MCh (10(-8.5)-10(-7.0) mol/kg) to seven mechanically ventilated pigs. Changes in CSA of bronchi of varying baseline size (1–10 mm diam) were determined by using a customized image processing software package (VIDA) based on a user-directed computer-adjusted edge-finding algorithm. MCh induced dose-dependent decreases in CSA, which were paralleled by increases in airway opening pressure at higher doses of MCh; at lower doses of MCh, decreases in CSA of smaller airways were detected without concomitant changes in airway opening pressure. Changes in CSA were heterogeneous and variable, especially in the smaller airway ranges. The results of the present study support the concept that UHRCT can be used in conjunction with bolus challenges to effectively determine dose-response changes in airway caliber in both large and small airways. This technique provides data that may not be reflected by conventional lung function measurements and, hence, is a useful tool to study airway reactivity.
Effect of exercise on autonomic mechanisms of baroreflex control of heart rate
Authors: O'Leary D. S. , Seamans D. P.
Published: December 2017

We tested whether moderate dynamic exercise alters baroreflex control of heart rate (HR) in conscious dogs and whether the autonomic mechanisms mediating arterial baroreflex control of HR differ in the two settings of rest and exercise. Conscious, chronically instrumented dogs were studied during rest and moderate treadmill exercise (6.4 kpm, 10% grade). Sustained changes in mean arterial pressure (MAP) were induced by graded intravenous infusions of phenylephrine and nitroglycerine. Baroreflex HR sensitivity was assessed as the slope of the linear regression between MAP and HR. Responses to increases and decreases in MAP were analyzed separately. Studies were repeated after muscarinic (atropine, 0.2 mg/kg iv) or beta-adrenergic (propranolol, 2.0 mg/kg iv) blockade during rest and exercise. During control experiments both at rest and during exercise, baroreflex changes in HR were greater in response to decreases than to increases in MAP. Experiments performed after separate cardiac autonomic blockade revealed that at rest baroreflex-induced bradycardia occurs via parasympathetic activation but tachycardia occurs via a combined parasympathetic inhibition-sympathetic activation. During exercise, whereas the magnitude of baroreflex responses was unchanged compared with rest, the autonomic mechanisms mediating the baroreflex changes in HR were altered. In this setting, baroreflex tachycardia and bradycardia occur via modulation of both parasympathetic and sympathetic tone.
Effect of common vasodilators on lung microvascular permeability
Authors: Swanson J. A. , Kern D. F.
Published: December 2017

The effect of papaverine on the albumin permeability-surface area product (PS), reflection coefficient (sigma), and capillary filtration coefficient (Kf) was examined in isolated rabbit lungs. Because PS and Kf are functions of vascular surface area and permeability, we also compared papaverine with two other means of maximizing lung surface area: isoproterenol (1 x 10(-7) M) and a mild increase in vascular pressure. Only lungs perfused with 0.1 mg/ml papaverine were significantly different from control. PS increased from control (2.80 +/- 0.16 to 5.53 +/- 0.20 ml.min-1.g dry lung-1 x 10(-2), whereas sigma decreased from control (0.92 +/- 0.01 to 0.78 +/- 0.03). Kf after papaverine was significantly lower than baseline predrug Kf (5.60 +/- 0.78 to 4.56 +/- 0.53 ml.s-1.cmH2O-1.g dry lung-1 x 10(-3). However, this group's predrug Kf was higher than that of any other group. Our results indicate that papaverine increases albumin permeability and decreases endothelial selectivity. The isolated perfused lung appears fully recruited, because Kf and PS did not increase with isoproterenol or increased vascular pressure. Papaverine should be used with caution in the Ringer-perfused lung.
Mechanical action of the internal intercostal muscles in dogs
Authors: DiMarco A. F. , Supinski G. S. , Simhai B. , Romaniuk J. R.
Published: December 2017

The pattern of electrical activation and muscle length changes of the internal intercostal (II) muscles (9th or 10th interspace) of the lower rib cage were evaluated in supine anesthetized dogs. Studies were performed during resting breathing and expiratory threshold loading. Results were compared with simultaneous measurements of the better-studied triangularis sterni muscle (4th interspace). In general, both muscles lengthened with passive inflation and shortened with passive deflation. During resting breathing, both the II and TS muscles were electrically active and shortened below resting length, 7.7 +/- 1.6% (SE) and 5.3 +/- 1.7%, respectively. With the addition of positive end-expiratory pressure, the degree of electrical activation and muscle shortening increased progressively for both muscles, although to a somewhat greater extent for II muscles. Isolated denervation of the II muscles eliminated their shortening during resting breathing and often resulted in muscle lengthening, indicating that II muscle shortening was secondary to its own activation. Expiration was associated with lateral inward movement of the lower rib cage below its relaxation position. This motion was not significantly affected by abdominal muscle section but was markedly reduced by bilateral II denervation (7th-11th spaces). Our results indicate that the II muscles of the lower rib cage 1) are electrically active and shorten below resting length during resting breathing, 2) respond to positive end-expiratory pressure by increasing their level of activation and degree of shortening, and 3) are primarily responsible for inward lateral motion of the lower rib cage below its relaxation position during expiration.
Substrate oxidation capacity in rodent skeletal muscle: effects of exposure to zero gravity
Authors: Baldwin K. M. , Herrick R. E. , McCue S. A.
Published: December 2017

A study was conducted, as part of the integrated National Aeronautics and Space Administration Space Life Sciences 1 mission flown in June of 1991, to ascertain the effects of 9 days of exposure to zero gravity on the capacity of rodent skeletal muscle fiber types to oxidize either [14C]pyruvate or [14C]palmitate under state 3 metabolic conditions, i.e., nonlimiting amounts of substrate and cofactors. In addition, activity levels of marker enzymes of the tricarboxylic acid cycle, malate shuttle, and beta-oxidation were measured. Results showed that significant differences in muscle weight occurred in both the predominantly slow vastus intermedius and predominantly fast vastus lateralis of flight vs. control groups (P < 0.05). Total protein content of the muscle samples was similar between groups. Both pyruvate oxidation capacity and the marker oxidative enzymes were not altered in the flight relative to control animals. However, the capacity to oxidize long-chain fatty acids was significantly reduced by 37% in both the high- and low-oxidative regions of the vastus muscle (P < 0.05). Although these findings of a selective reduction in fatty acid oxidation capacity in response to spaceflight are surprising, they are consistent with previous findings showing 1) an increased capacity to take up glucose and upregulate glucose transporter proteins and 2) a marked accumulation of triglycerides in the skeletal muscles of rats subjected to states of unloading. Thus, skeletal muscle of animals exposed to non-weight-bearing environments undergo subcellular transformations that may preferentially bias energy utilization to carbohydrates.
Vasoconstrictor properties of rat aorta are diminished by hindlimb unweighting
Authors: Delp M. D. , Holder-Binkley T. , Laughlin M. H. , Hasser E. M.
Published: December 2017

Prolonged bed rest and exposure to weightlessness in humans result in cardiovascular alterations that are characterized by orthostatic intolerance and decreased exercise capacity. Modifications of cardiovascular function have been suggested to be causally related to changes in peripheral vascular reactivity. Rat hindlimb unweighting (HU) was used as an animal model to determine whether prolonged decreases in weight-bearing activity induce changes in vasoreactivity of peripheral arterial vessels. Responses to vasoactive compounds were examined in vitro using isolated abdominal and thoracic aortic rings. Maximal isometric contractile tension evoked by the vasoconstrictors KCl (10–100 mM), norepinephrine (NE; 10(-9)-10(-4) M), phenylephrine (10(-9)-10(-4) M), arginine vasopressin (10(-13)-3 x 10(-5) M), and CaCl2 (10(-6)-10(-2) M) was lower in abdominal aortic rings from HU rats. Sensitivity [agonist concentration that produced 50% of maximal vasoconstrictor response (EC50)] to KCl was enhanced in segments from HU animals but was not different for the other constrictors. Maximal contractile responses of thoracic aortic rings to KCl (10–100 mM) and NE (10(-9)-10(-4) M) were also attenuated by HU. In abdominal aortic rings preconstricted with 10(-4) M NE, maximal vasodilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and 8-bromoguanosine 3',5'-cyclic monophosphate (10(-6)-10(-2) M) were greater in vessel rings from HU rats. However, with 10(-7) M NE preconstriction, maximal dilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and acetylcholine (10(-9)-10(-4) M) were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of central respiratory muscle fatigue in endurance exercise in normal subjects
Authors: Marciniuk D. , McKim D. , Sanii R. , Younes M.
Published: December 2017

The role of central respiratory muscle fatigue in determining endurance time (ET) of steady-state ergometry, ventilation (VE), and breathing pattern during exhaustive submaximal exercise is not known. Six normal subjects exercised on a cycle ergometer to exhaustion at 72–82% of maximal power output on three occasions. During the second test, inspiratory muscle load was reduced (approximately 50% of baseline load) for all but the last 3 min of exercise. ET was determined, and VE, tidal volume (VT), respiratory rate (f), and sense of breathing effort (Borg scale) were assessed at different points during the assisted exercise and compared with the values obtained at the same time in identical tests without assist, carried out before and after the assisted test (different days). Borg scale rating was less and there was a nonsignificant trend for VT and VE to be higher and for f to be lower when the assist was in place than at the same time during the unassisted runs. In the last 3 min of exercise, when the respiratory load was comparable (assist removed) but ventilatory work history was different, there were no significant differences in sense of respiratory effort, VE, VT, or f between the experimental and control tests, and ET was also similar. We conclude that central respiratory muscle fatigue plays no role in determining ET, sense of respiratory effort, or breathing pattern in normal subjects during exhaustive submaximal exercise.
Developmental pattern of hypercapnic and hypoxic ventilatory responses from childhood to adulthood
Authors: Marcus C. L. , Glomb W. B. , Basinski D. J. , Davidson S. L. , Keens T. G.
Published: December 2017

The developmental pattern of ventilatory responses, through childhood and puberty into adulthood, is not known. Therefore we studied hypercapnic (HCVR) and hypoxic ventilatory responses (HOVR) in 59 subjects (29 males and 30 females) 4–49 yr of age, of whom 35 were children ( < 18 yr old). There was a significant correlation between HCVR and weight (r = 0.33, P < 0.02), vital capacity (r = 0.30, P < 0.05), and body surface area (r = 0.30, P < 0.05) but not height (r = 0.22, NS). There was no correlation between HOVR and any of the correcting factors. To account for disparities in body size, volume-related results were scaled for body weight. The HCVR corrected for weight (HCVR/WT) decreased with age (r = -0.57, P < 0.001). HCVR/WT was significantly higher in children than in adults (0.056 +/- 0.024 vs. 0.032 +/- 0.015 l.kg-1 x min-1. Torr end-tidal PCO2-1, P < 0.001). The (tidal volume/inspiratory duration)/weight, respiratory rate, and heart rate responses to hypercapnia were increased in the children, and the CO2 threshold was lower (36 +/- 5 vs. 40 +/- 6 Torr, P < 0.05). Similarly, the HOVR corrected for weight (HOVR/WT) decreased with age (r = 0.34, P < 0.05), and HOVR/WT was significantly higher in children than in adults (-0.035 +/- 0.017 vs. -0.024 +/- 0.016 l.kg-1 x min-1.% arterial O2 saturation-1, P < 0.02). The respiratory rate and heart rate responses to hypoxia were increased in the children. We conclude that rebreathing HCVR and HOVR are higher during childhood than during adulthood.
Relationship between intracellular pH, extracellular pH, and ventilation during dilution acidosis
Authors: Kasserra C. E. , Jones D. R. , Kushmerick M. J.
Published: December 2017

Previous experiments showed that acute hyperosmolality results in an extracellular acidosis that does not stimulate respiratory compensation (C.E. Kasserra, D. R. Jones, and M. R. Hughes. Respir. Physiol. 85: 383–393, 1991). The data suggested that development of the extracellular dilution acidosis would also result in a concomitant intracellular contraction alkalosis. The effects of acute hyperosmolality and lactacidosis on systemic intracellular pH (pHi) were studied in the conscious Pekin duck in an effort to separate the effects of pHi and extracellular pH (pHe) on ventilatory control. Brain pH was also measured during systemic hyperosmolality to determine the relationship between blood and brain pHi. Hyperosmolality caused a concurrent extracellular acidosis and intracellular alkalosis in pectoral muscle, whereas lactic acid infusion decreased both pHe and pHi. Ventilation was stimulated only during lactacidosis and did not change during hyperosmolality. Brain pHi did not show a consistent significant increase in response to systemic hyperosmolality over 1 h but did show a trend toward an alkalosis. Measurement of high-energy phosphate metabolites (phosphocreatine, ATP, and Pi) indicated an increase of metabolic rate during hyperosmolality. With the assumption that similar pHi changes were occurring in chemoreceptive cells, the results suggest that ventilation was responding to pHi changes and that much of the depressive response to acute hyperosmotic disturbance was peripherally generated.
Dynamically Interacting Processes Underlie Synaptic Plasticity in a Feedback Pathway
Authors: Oswald Anne-Marie M. , Lewis John E. , Maler Leonard
Published: December 2017

Descending feedback is a common feature of sensory systems. Characterizing synaptic plasticity in feedback inputs is essential for delineating the role of feedback in sensory processing. In this study, we demonstrate that multiple interacting processes underlie the dynamics of synaptic potentiation in one such sensory feedback pathway. We use field recording and modeling to investigate the interaction between the transient high-magnitude potentiation (200–300%) elicited during tetanic stimulation of the feedback pathway and the lower magnitude posttetanic potentiation (PTP; ∼30%) that slowly decays on cessation of the tetanus. The amplitude of the observed transient potentiation is graded with stimulus frequency. In contrast, the induction of PTP has a stimulus frequency threshold between 1 and 5 Hz, and its amplitude is independent of stimulus frequency. We suggest that the threshold for PTP induction may be linked to a minimum level of sustained potentiation (MSP) during repetitive trains of stimuli. We have developed a novel model that describes the interaction between the transient plasticity observed during train stimulation and the generation of PTP. The model combines a multiplicative, facilitation-depression-type ( FD) model that describes the transient plasticity, with an enzymatic network that describes the dynamics of PTP. The model links transient plasticity to PTP through an input term that reflects MSP. The stratum fibrosum–pyramidal cell (StF-PC) synapse investigated in this study is the terminus of a feedback pathway to the electrosensory lateral line lobe (ELL) of a weakly electric gymnotiform fish. Dynamic plasticity at the StF-PC synapse may contribute to the putative role of this feedback pathway as a sensory searchlight.
Inhibitory Interactions Between Ferret Thalamic Reticular Neurons
Authors: Shu Yousheng , McCormick David A.
Published: December 2017

The thalamic reticular nucleus (nRt) provides an important inhibitory input to thalamic relay nuclei and is central in the generation of both normal and abnormal thalamocortical activities. Although local inhibitory interactions between these neurons may play an important role in controlling thalamocortical activities, the physiological features of this interaction have not been fully investigated. Here we sought to establish the nature of inhibitory interaction between nRt neurons with intracellular and extracellular recordings in slices of ferret nRt maintained in vitro. In many nRt neurons, intracellular recordings revealed spontaneous inhibitory postsynaptic potentials (IPSPs). In addition, the local excitation of nRt cells with glutamate led to the generation of IPSPs in the intracellularly recorded nRt neuron. These evoked IPSPs exhibited an average reversal potential of −72 mV and could be blocked by picrotoxin, a GABAA-receptor antagonist. These results indicate that nRt neurons interact locally through the activation of GABAA receptor-mediated inhibitory postsynaptic potentials. This lateral inhibition may play an important role in controlling the responsiveness of these cells to cortical and thalamic excitatory inputs in both normal and abnormal thalamocortical function.
Predictive Motor Learning of Temporal Delays
Authors: Witney Alice G. , Goodbody Susan J. , Wolpert Daniel M.
Published: December 2017

Anticipatory responses can minimize the disturbances that result from the action of one part of the body on another. Such a predictive response is evident in the anticipatory increase in grip force seen when one hand pulls on an object held in the other hand, thereby preventing the object from slipping. It is postulated that such a response depends on predicting the consequences of the descending motor command, as signaled by efference copy, using an internal model of both one's own body and the object. Here we investigate how the internal model learns the temporal consequences of the motor command. We employed two robots to simulate a virtual object held in one hand and acted on by the other. Delays were introduced between the action of one hand on the object and the effects of this action on the other hand. An initial reactive grip force response to the delayed load decayed with the development of appropriate anticipatory grip force modulation. However, no predictive modulation was seen when the object's movement was not generated by the subject, even when the motion was cued by a tone. These results suggest that, when an internal model learns new temporal relationships between actions and their consequences, this learning involves generating a novel response rather than adapting the original predictive response.
Voltage Dependence of the Glycine Receptor–Channel Kinetics in the Zebrafish Hindbrain
Authors: Legendre Pascal
Published: December 2017

Electrophysiological recordings of outside-out patches to fast-flow applications of glycine were made on patches derived from the Mauthner cells of the 50-h-old zebrafish larva. As for glycinergic miniature inhibitory postsynaptic currents (mIPSCs), depolarizing the patch produced a broadening of the transient outside-out current evoked by short applications (1 ms) of a saturating concentration of glycine (3 mM). When the outside-out patch was depolarized from −50 to +20 mV, the peak current varied linearly with voltage. A 1-ms application of 3 mM glycine evoked currents that activated rapidly and deactivated biexponentially with time constants of ≈5 and ≈30 ms (holding potential of −50 mV). These two decay time constants were increased by depolarization. The fast deactivation time constant increased e-fold per 95 mV. The relative amplitude of the two decay components did not significantly vary with voltage. The fast component represented 64.2 ± 2.8% of the total current at −50 mV and 54.1 ± 10% at +20 mV. The 20–80% rise time of these responses did not show any voltage dependence, suggesting that the opening rate constant is insensitive to voltage. The 20–80% rise time was 0.2 ms at −70 mV and 0.22 ms at +20 mV. Responses evoked by 100–200 ms application of a low concentration of glycine (0.1 mM) had a biphasic rising phase reflecting the complex gating behavior of the glycine receptor. The time constant of these two components and their relative amplitude did not change with voltage, suggesting that modal shifts in the glycine-activated channel gating mode are not sensitive to the membrane potential. Using a Markov model to simulate glycine receptor gating behavior, we were able to mimic the voltage-dependent change in the deactivation time course of the responses evoked by 1-ms application of 3 mM glycine. This kinetics model incorporates voltage-dependent closing rate constants. It provides a good description of the time course of the onset of responses evoked by the application of a low concentration of glycine at all membrane potentials tested.
Calcium Dynamics Underlying Pacemaker-Like and Burst Firing Oscillations in Midbrain Dopaminergic Neurons: A Computational Study
Authors: Amini B. , Clark J. W. , Canavier C. C.
Published: December 2017

A mathematical model of midbrain dopamine neurons has been developed to understand the mechanisms underlying two types of calcium-dependent firing patterns that these cells exhibit in vitro. The first is the regular, pacemaker-like firing exhibited in a slice preparation, and the second is a burst firing pattern sometimes exhibited in the presence of apamin. Because both types of oscillations are blocked by nifedipine, we have focused on the slow calcium dynamics underlying these firing modes. The underlying oscillations in membrane potential are best observed when action potentials are blocked by the application of TTX. This converts the regular single-spike firing mode to a slow oscillatory potential (SOP) and apamin-induced bursting to a slow square-wave oscillation. We hypothesize that the SOP results from the interplay between the L-type calcium current (ICa,L) and the apamin-sensitive calcium-activated potassium current ( IK,Ca,SK). We further hypothesize that the square-wave oscillation results from the alternating voltage activation and calcium inactivation of ICa,L. Our model consists of two components: a Hodgkin-Huxley-type membrane model and a fluid compartment model. A material balance on Ca2+is provided in the cytosolic fluid compartment, whereas calcium concentration is considered constant in the extracellular compartment. Model parameters were determined using both voltage-clamp and calcium-imaging data from the literature. In addition to modeling the SOP and square-wave oscillations in dopaminergic neurons, the model provides reasonable mimicry of the experimentally observed response of SOPs to TEA application and elongation of the plateau duration of the square-wave oscillations in response to calcium chelation.
Regional Distribution of Ionic Currents and Membrane Voltage Responses of Type II Hair Cells in the Vestibular Neuroepithelium
Authors: Weng Tianxiang , Correia Manning J.
Published: December 2017

Basolateral ionic currents and membrane voltage responses were studied in pigeon vestibular type II hair cells using a thin slice through either the semicircular canal (SCC) crista or utricular macular epithelium. Whole cell tight-seal patch-clamp recording techniques were used. Current-clamp and voltage-clamp studies were carried out on the same cell. One hundred ten cells were studied in the peripheral (Zone I) and central (Zone III) zones of the SCC crista, and 162 cells were studied in the striolar (S Zone) and extrastriolar (ES Zone) zones of the utricular macula. One of the major findings of this paper is that hair cells with fast activation kinetics of their outward currents are found primarily in one region of the SCC crista andutricular macula, whereas hair cells with slow activation kinetics are found in a different region. In Zone I of the crista, 95% of the cells have fast activation kinetics (“fast” cells) and in Zone III of the crista, 86% of the cells have slow activation kinetics (“slow” cells). In the utricular macula slice, 100% of the cells from the S Zone are slow cells, whereas 86% of the cells from the ES Zones are fast cells. Oscillation frequency ( f) and quality factor ( Q) of the damped oscillations of the membrane potential during extrinsic current injections were studied in hair cells in the different regions. The slow cells in Zone III and in the S Zone have a statistically significantly lower f, as a function of the amplitude of injected current, when compared with the fast cells in Zone I and the ES Zone. Although Q varied over a small range and was <2.6 for all cells tested, there was a statistically significant difference between Q for the membrane oscillations of the slow cells and fast cells in response to a range of current injections.
Synaptic Modulation Contributes to Firing Pattern Generation in Jaw Motor Neurons During Rejection of Seaweed in Aplysia kurodai
Authors: Nagahama Tatsumi , Narusuye Kenji , Arai Hidekazu
Published: December 2017

Japanese species, Aplysia kurodai, feeds well on Ulva but rejects Gelidium ( Geli.) or Pachydictyon ( Pach.) with different rhythmic patterned movements of the jaws and radula. During ingestion the jaws open at the radula-protraction phase and remain half open at the initial phase of the radula-retraction, whereas during rejection the jaws open similarly but start to close immediately after the onset of the radula-retraction. These can be induced not only by the natural seaweed but by the extract solutions. We previously showed that the change of the patterned jaw movements from the ingestion to the rejection may result from the decrease in the delay of the firing onset of the jaw-closing (JC) motor neurons during their depolarization. This diminished delay produces a phase advance relative to the radula-retraction phase. In that study, we showed that during ingestion the buccal multiaction (MA) neurons may generate the delay of firing onset of the JC motor neurons by producing monosynaptic inhibitory postsynaptic potentials (IPSPs) during the initial portion of their depolarization. In the present experiments, the firing patterns in the MA neurons induced by application of the Geli. or Pach. extract to the lips were explored in the semi-intact preparations. During the Pach. response the duration and the firing frequency of the MA firing at each depolarizing phase were decreased in comparison with the Ulvaresponse. No decreases in the MA firing were observed during the Geli. response, suggesting that the similar patterned jaw movements during rejection of Geli. and Pach. may be generated by different neural mechanisms. Moreover, the size of the MA-induced IPSP in the JC motor neurons was largely decreased by application of the Geli. or Pach. extract to the lips in the reduced preparations consisting of the tentacle-lips and the cerebral-buccal ganglia. Voltage-clamp experiments on the JC motor neurons showed that the size of synaptic current induced by the MA spikes was decreased by application of these solutions to the lips. The decrease was induced when the buccal ganglia were bathed in a solution to block polysynaptic pathways. These results suggest that the advance of the onset of the JC firing at each depolarizing phase during the Geli. or Pach. response may be mainly or partly caused by the decrease in the size of the MA-induced IPSP in the motor neurons. Modulatory action of cerebral neurons or peripheral afferent neurons in the lip region may contribute to this synaptic plasticity.
Gustatory Neuron Types in Rat Geniculate Ganglion
Authors: Lundy Robert F. , Contreras Robert J.
Published: December 2017

We used extracellular single-cell recording procedures to characterize the chemical and thermal sensitivity of the rat geniculate ganglion to lingual stimulation, and to examine the effects of specific ion transport antagonists on salt transduction mechanisms. Hierarchical cluster analysis of the responses from 73 single neurons to 3 salts (0.075 and 0.3 M NaCl, KCl, and NH4Cl), 0.5 M sucrose, 0.01 M HCl, and 0.02 M quinine HCl (QHCl) indicated 3 main groups that responded best to either sucrose, HCl, or NaCl. Eight narrowly tuned neurons were deemed sucrose-specialists and 33 broadly tuned neurons as HCl-generalists. The NaCl group contained three identifiable subclusters: 18 NaCl-specialists, 11 NaCl-generalists, and 3 QHCl-generalists. Sucrose- and NaCl-specialists responded specifically to sucrose and NaCl, respectively. All generalist neurons responded to salt, acid, and alkaloid stimuli to varying degree and order depending on neuron type. Response order was NaCl > HCl = QHCl > sucrose in NaCl-generalists, HCl > NaCl > QHCl > sucrose in HCl-generalists, and QHCl = NaCl = HCl > sucrose in QHCl-generalists. NaCl-specialists responded robustly to low and high NaCl concentrations, but weakly, if at all, to high KCl and NH4Cl concentrations after prolonged stimulation. HCl-generalist neurons responded to all three salts, but at twice the rate to NH4Cl than to NaCl and KCl. NaCl- and QHCl-generalists responded equally to the three salts. Amiloride and 5-( N,N-dimethyl)-amiloride (DMA), antagonists of Na+channels and Na+/H+exchangers, respectively, inhibited the responses to 0.075 M NaCl only in NaCl-specialist neurons. The K+channel antagonist, 4-aminopyridine (4-AP), was without a suppressive effect on salt responses, but, when applied alone in solution, it evoked a response in many HCl-generalists and one QHCl-generalist neuron so tested. Of the 39 neurons tested for their sensitivity to temperature, 23 responded to cooling and chemical stimulation, and 20 of these neurons were HCl-generalists. Moreover, the responses to the four standard stimuli were reduced progressively at lower temperatures in HCl- and QHCl-generalist neurons, but not in NaCl-specialists. Thus sodium channels and Na+/H+exchangers appear to be expressed exclusively on the membranes of receptor cells that synapse with NaCl-specialist neurons. In addition, cooling sensitivity and taste-temperature interactions appear to be prominent features of broadly tuned neuron groups, particularly HCl-generalists. Taken all together, it appears that lingual taste cells make specific connections with afferent fibers that allow gustatory stimuli to be parceled into different input pathways. In general, these neurons are organized physiologically into specialist and generalist types. The sucrose- and NaCl-specialists alone can provide sufficient information to distinguish sucrose and NaCl from other stimuli, respectively.
Visual Stimulus–Dependent Changes in Interhemispheric EEG Coherence in Humans
Authors: Knyazeva M. G. , Kiper D. C. , Vildavski V. Y. , Despland P. A. , Maeder-Ingvar M. , Innocenti G. M.
Published: December 2017

We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects ( n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.