bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion
Authors: Glenny R. W. , Bernard S. , Brinkley M.
Published: December 2017

Estimations of dog lung, pig heart, and pig kidney regional perfusion by use of fluorescent-labeled microspheres were compared with measurements obtained with standard radiolabeled microspheres. Pairs of radio- and fluorescent-labeled microspheres (15 microns diam, 6 colors) were injected into a central vein of a supine anesthetized dog and the left ventricle of three supine anesthetized pigs while reference blood samples were simultaneously withdrawn from a femoral artery in the pigs. The lungs were cubed into approximately 2 cm3 pieces (n = 1,510). Each pig heart and kidney was cubed into approximately 1-g pieces (total n = 192 and 120, respectively). The radioactivity of each organ piece and reference blood sample was determined using a scintillation counter with count rates corrected for decay, background, and spillover. Tissue samples and reference blood samples were digested with KOH and filtered and the fluorescent dye was extracted with a solvent, or the dye was extracted from lung tissue without filtering. The fluorescence of each sample was determined for each color by use of an automated spectrophotometer. Perfusion was calculated for each organ piece from both the radioactivity and fluorescence. Correlation between flow determined by radio- and fluorescent-labeled microspheres was as follows: r = 0.96 +/- 0.01 (SD) (lung, filtered, n = 588), r = 0.99 +/- 0.00 (lung, nonfiltered, n = 710), r = 0.95 +/- 0.02 (heart, filtered), and r = 0.96 +/- 0.02 (kidney, filtered). Compared with colored microspheres, methods for quantitating fluorescent-labeled microspheres are more sensitive, less labor intensive, and less expensive. Fluorescent-labeled microspheres provide a new nonradioactive method for single and repeated measurement of regional organ perfusion.
Nature of the mammalian ciliary metachronal wave
Authors: Wong L. B. , Miller I. F. , Yeates D. B.
Published: December 2017

The temporal and spatial coordination of ciliary beat (metachronicity) is fundamental to effective mucociliary transport. Metachronal wave period (MWP) and ciliary beat frequency (CBF) of fresh excised sheep and canine tracheal epithelial tissues were measured with the use of a newly developed alternating focal spot laser light scattering system. MWP was determined from cross correlation of the heterodyne signals from the alternating focal spots. CBF was determined by autocorrelation of the heterodyne signals from each of the spots. MWP and CBF were measured in four sheep tracheal epithelial tissues with the use of longitudinal interfocal spot distances of 6 and 18 microns. In three canine tracheal epithelial tissues MWP and CBF were measured both longitudinally and circumferentially with interfocal spot distances of 5, 15, 65, 87, and 96 microns. For the sheep tracheal epithelial tissues the mean CBF was 5.9 +/- 0.4 Hz (mean of means; range 3.6 +/- 0.5 to 9.9 +/- 1.5 Hz), whereas the mean MWPs for 6- and 18-microns interfocal spot distances were 0.50 +/- 0.1 and 0.47 +/- 0.1 s, respectively. For the canine tracheal epithelial tissues the mean CBF was 4.0 +/- 0.2 Hz (2.0 +/- 0.8 to 7.2 +/- 3.2 Hz), whereas the mean longitudinal MWP was 1.5 s and the mean circumferential MWP was 2.1 s. Geometric combination of the MWP components leads to a derived MWP of 2.6 s with a propagation direction of 54 degrees with respect to the longitudinal axis of the trachea. MWP was found to be episode modulated with 12- to 20-min intervals in the longitudinal direction, but modulation was not as apparent in the circumferential direction. These data suggest that MWP and CBF are regulated by separate intracellular, intercellular, and intraciliary mechanisms.
Effects of rapid-eye-movement sleep on the apneic threshold in dogs
Authors: Xi L. , Smith C. A. , Saupe K. W. , Henderson K. S. , Dempsey J. A.
Published: December 2017

We determined whether the apneic threshold after active hyperventilation was different in rapid-eye-movement (REM) vs. non-REM (NREM) sleep. Sleeping dogs were repeatedly exposed to 35–45 s of hypoxia of varying severity (end-tidal PO2 40–60 Torr) that was abruptly terminated with 100% O2. Changes in breathing pattern after brief hypoxia were compared with those after a normoxia-to-hyperoxia transition, i.e., control conditions. In NREM sleep, hypoxic hyperventilation was consistently followed by central apnea, the duration of which was linearly related to the corresponding hypocapnia and/or increase in tidal volume (VT) during hypoxia. After hypoxia, expiratory duration averaged 3.5 x control value at -5-Torr change in end-tidal PCO2 and twofold increase in VT; mean expiratory duration was 5 x control value at -10-Torr change in end-tidal PCO2 and fourfold increase in VT. In REM sleep, central apnea of varying duration did occur on occasion after brief hypoxic hyperventilation, but there was no systematic relationship with magnitude of hypocapnia or increase in VT. Breathing pattern during or after hypoxia in REM was not related to temporal changes in either eye movement density or electroencephalogram frequency. Thus, in contrast to NREM sleep, in REM sleep ("phasic" or "tonic") a posthyperventilation apneic threshold was not present. We attribute this effect of REM to 1) a reduced VT response to hypoxia that would minimize inhibitory "memory" effect from lung stretch and 2) attenuated inhibitory response to any given magnitude of hypocapnia or increased VT. Active hyperventilation-induced apneic threshold may be "masked" by actions of nonchemoreceptor and nonmechanoreceptor inputs affecting respiratory motor output in REM sleep. These data are consistent with the relative absence of central apnea and periodic breathing in humans in REM sleep.
Exogenous carbohydrate oxidation from different carbohydrate sources during exercise
Authors: Saris W. H. , Goodpaster B. H. , Jeukendrup A. E. , Brouns F. , Halliday D. , Wagenmakers A. J.
Published: December 2017

The exogenous carbohydrate (CHO) oxidation of naturally enriched [13C]CHO sources with different solubilities was studied during cycling exercise (150 min, 60% maximum work output). Moreover, the effect of adding a 13C tracer with different physical properties than the tracee on exogenous CHO oxidation was investigated. Test solutions (28.5 ml/kg body wt) were water for control of 13C background, 15% soluble partially hydrolyzed corn starch (SOL), 15% insoluble corn starch (In-SOL), and 15% InSOL with [13C6]glucose as tracer. Both the mean and peak exogenous oxidation rates were significantly greater (P < 0.05) in the SOL trial than in the InSOL trial (mean oxidation rate, 0.84 +/- 0.21 and 0.50 +/- 0.15 g/min, respectively; peak oxidation rate, 1.10 +/- 0.18 and 0.81 +/- 0.25 g/min, respectively). The amount of the ingested CHO that was oxidized was significantly higher (P < 0.05) in the SOL trial (126 +/- 31 g) than in the InSOL trial (75 +/- 25 g). When we added an extrinsic tracer ([13C]glucose), the apparent mean and peak oxidation rates of the trial with InSOL and [13C6]glucose were significantly (P < 0.05) higher (0.91 +/- 0.30 and 1.23 +/- 0.41, respectively) than the InSOL values. These results 1) indicate that the addition of the soluble [13C]glucose tracer to an insoluble starch tracee leads to overestimation of the exogenous CHO oxidation rates and 2) suggest that soluble CHO is oxidized at a higher rate during exercise than isocaloric insoluble CHO.
Nitric oxide inhibition varies with hemoglobin saturation
Authors: Iwamoto J. , Morin F. C.
Published: December 2017

Endothelium-derived nitric oxide (NO) appears to be involved in the regulation of pulmonary vascular tone by O2. We hypothesized that the ability of blood to inhibit the vasodilation caused by NO would vary inversely with the saturation of hemoglobin by O2. To test this hypothesis, we used the pulmonary circulation of the unanesthetized fetal lamb as a bioassay for NO-induced vasodilation. Two to 3 days before the experiment, the main pulmonary artery, left atrium, carotid artery, and trachea of the fetus were catheterized and an ultrasonic blood flow transducer was placed around the proximal portion of the left pulmonary artery. On the day of the experiment, NO solution was prepared by bubbling 10% NO-90% N2 gas mixture in saline. This solution was injected into the fluid-filled potential air spaces of the fetal lungs via the trachea. At the highest dose (0.8 mumol), NO increased pulmonary blood flow fourfold and decreased pulmonary vascular resistance similarly. The dose-response curve for NO was similar to those obtained from isolated pulmonary blood vessels and gas-ventilated animals. Mixing NO solution with maternal arterial blood before injection decreased the effect of NO, and mixing it with venous blood virtually eliminated the effect. The decrease in fetal pulmonary vascular resistance caused by NO was inhibited by blood in inverse proportion to the saturation of hemoglobin with O2 in the blood (R2 = 0.93, P < or = 0.0001), confirming our hypothesis.
Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms
Authors: Talmadge R. J. , Roy R. R.
Published: December 2017

A new technique for the sodium dodecyl sulfate-polyacrylamide gel electrophoretic separation of rat skeletal muscle myosin heavy-chain (MHC) isoforms is presented. This technique allows for the separation of the four identified MHC isoforms known to be present in adult rat skeletal muscle. These types of MHC are commonly called I, IIa, IIx or IId, and IIb. The procedure can be performed using minigel electrophoresis systems and does not involve preparation of gradient-separating gels or the use of special cooling devices. The procedure accommodates both silver and Coomasie Blue staining. Thus the procedure is simple to perform and highly repeatable, providing high-resolution separation of MHC protein isoforms. The percent composition of the four adult MHCs in rat soleus, medial gastrocnemius, diaphragm, and levator ani muscles by use of this procedure and Coomasie Blue staining is similar to that previously reported. This new technique provides a novel and easy-to-perform method for the separation of rat skeletal muscle MHC isoforms.
Experimental and biological variation of three-dimensional transcranial Doppler measurements
Authors: Thomsen L. L. , Iversen H. K.
Published: December 2017

A new transcranial Doppler system (3-D Transscan, Eden Medizinische Elektronik) was evaluated in relation to sex, age, intersubject, interobserver, side-to-side, and day-to-day variation. Fifty-eight healthy volunteers participated (aged 18–80 yr). Mean velocity was higher in females than in males and decreased with age. The coefficient of variation in the middle cerebral artery was 26% between subjects, 20% between sides, 16% between days, 13% between observers, and 7% during 5 min. The coefficient of variation was higher in the anterior and posterior cerebral arteries. Bruits were heard in 35 subjects, 24 females and 11 males (P = 0.002). When middle cerebral artery velocity was monitored, high- and low-frequency oscillations were found, with a mean frequency of 5 and 1.6/min, respectively. These variations underline the necessity of standardized conditions and very carefully matched control groups in studies using transcranial Doppler. This is especially important when expected changes are small and easy to overlook, as in studies of normal physiological responses and migraine.
Effect of aerobic training on baroreflex regulation of cardiac and sympathetic function
Authors: Sheldahl L. M. , Ebert T. J. , Cox B. , Tristani F. E.
Published: December 2017

To investigate the effect of aerobic exercise training on baroreflex regulation of muscle sympathetic nerve activity (MSNA) and cardiac R-R intervals in a middle-aged to older population, 10 healthy men > 40 yr of age underwent tests of autonomic function before and after 12 wk of high-intensity training. Cardiac and peripheral baroslopes were determined from the R-R interval vs. mean arterial pressure (MAP) and peroneal MSNA vs. diastolic pressure relationships, respectively, during sequential bolus injections of nitroprusside and phenylephrine. Maximal oxygen uptake increased (P < 0.05) 17% with training. Resting R-R interval increased (881 +/- 23 to 956 +/- 38 ms, P < 0.05), MAP decreased (96 +/- 2 to 91 +/- 3 mmHg, P < 0.05), and MSNA was unaltered (23.1 +/- 2.3 to 23.6 +/- 1.9 bursts/min) with training. Before and after training, respectively, cardiac baroslopes determined with decreasing (8.7 +/- 0.9 to 9.9 +/- 5.5 ms/mmHg) and increasing MAP (9.6 +/- 2.1 to 9.9 +/- 2.2 ms/mmHg) and the peripheral sympathetic baroslope (-3.3 +/- 0.4 to -3.5 +/- 0.6 bursts.min-1 x mmHg-1) did not differ. The results suggest that short-term aerobic training does not alter resting MSNA or neurocirculatory responses to baroreceptor challenges in middle-aged and older men.
Lung and chest wall mechanical properties before and after cardiac surgery with cardiopulmonary bypass
Authors: Barnas G. M. , Watson R. J. , Green M. D. , Sequeira A. J. , Gilbert T. B. , Kent J. , Villamater E.
Published: December 2017

From measurements of airway and esophageal pressures and flow, we calculated the elastance and resistance of the total respiratory system (Ers and Rrs), chest wall (Ecw and Rcw), and lungs (EL and RL) in 11 anesthetized-paralyzed patients immediately before cardiac surgery with cardiopulmonary bypass and immediately after chest closure at the end of surgery. Measurements were made during mechanical ventilation in the frequency and tidal volume ranges of normal breathing. Before surgery, frequency and tidal volume dependences of the elastances and resistances were similar to those previously measured in awake seated subjects (Am. Rev. Respir. Dis. 145: 110–113, 1992). After surgery, Ers and Rrs increased as a result of increases in EL and RL (P < 0.05), whereas Ecw and Rcw did not change (P > 0.05). EL and RL exhibited nonlinearities (i.e., decreases with increasing tidal volume) that were not seen before surgery, and RL showed a greater dependence on frequency than before surgery. The changes in RL or EL after surgery were not correlated with the duration of surgery or cardiopulmonary bypass time (P > 0.05). We conclude that 1) frequency and tidal volume dependences of respiratory system properties are not affected by anesthesia, paralysis, and the supine posture, 2) open-chest surgery with cardiopulmonary bypass does not affect the mechanical properties of the chest, and 3) cardiac surgery involving cardiopulmonary bypass causes changes in the mechanical behavior of the lung that are generally consistent with those caused by pulmonary edema induced by oleic acid (J. Appl. Physiol. 73: 1040–1046, 1992) and decreases in lung volume.
Roles of neutrophil elastase and superoxide anion in leukotriene B4-induced lung injury in rabbit
Authors: Yoshimura K. , Nakagawa S. , Koyama S. , Kobayashi T. , Homma T.
Published: December 2017

The effects of a competitive neutrophil elastase (NE) inhibitor, ONO-5046, and a recombinant human superoxide dismutase on leukotriene B4 (LTB4)-induced polymorphonuclear leukocyte (PMN)-mediated increase in microvascular permeability in isolated non-blood-perfused rabbit lungs were studied. Pulmonary microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (Kf) and the wet-to-dry lung weight ratio (W/D), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. NE activity in the perfusate was determined using a spectrophotometric method. The PMNs (2–3 x 10(8) cells) were added into the perfusate in all groups of lungs. Injection of LTB4 (5 micrograms) increased Kf and W/D without affecting pulmonary arterial or capillary pressure. The LTB4-induced lung injury was closely associated with the increase in NE activity in the perfusate. Infusion of ONO-5046 (1 or 10 mg.kg-1 x h-1) inhibited the LTB4-induced increases in Kf, W/D, and perfusate NE activity in a dose-dependent fashion. Infusion of recombinant human superoxide dismutase (80,000 U.kg-1 x h-1) attenuated the LTB4-induced increases in Kf and W/D, although it did not influence the elevation of perfusate NE activity induced by LTB4. These results suggest that both NE and superoxide anion play important roles in the LTB4-induced PMN-mediated increase in pulmonary microvascular permeability.
Intratracheal antioxidants attenuate exsanguination-induced bronchoconstriction in guinea pigs
Authors: Zhang H. Q. , Lai Y. L.
Published: December 2017

The role of oxygen radicals in exsanguination-induced bronchoconstriction (EIB) was investigated using intratracheal instillation of antioxidants. In series 1, 49 guinea pigs (331 +/- 6 g) were employed in the functional study. These animals were divided into seven groups: control, superoxide dismutase (SOD), catalase (CAT), erythrocytes (RBCs), N-[2-(2-oxo-1-imidazolindinyl)-ethyl]-N′-phenylurea (EDU), ruthenium red (RR), and systemic capsaicin pretreatment. SOD, CAT, RBCs, and EDU are antioxidants, whereas RR is a blocker of transmembrane Ca2+ fluxes. All agents except capsaicin were administered by intratracheal instillation 30 min before exsanguination; each animal of the last group received a 5-day subcutaneous capsaicin pretreatment. All animals were anesthetized, sternotomized, and exsanguinated. Before as well as 1–30 min after exsanguination, the maximal expiratory flow maneuver was performed and the minimal volume was obtained. In the control group, exsanguination caused gradual decreases in the maximal expiratory flow at 50% baseline total lung capacity, forced expiratory volume at 0.1 s, and total lung capacity as well as a gradual increase in the minimal volume, indicating that EIB becomes more severe with time. EIB was significantly ameliorated by intratracheal instillation of SOD, CAT, RBCs, EDU, and RR, and it was almost abolished by systemic capsaicin pretreatment. In series 2, however, inactivated CAT did not significantly affect EIB. We determined tracheal neutral endopeptidase (NEP) activity in 23 animals. Thirty minutes after exsanguination, there was a significant decrease in NEP activity in the control but not the CAT group. These results indicate that EIB is modulated by oxygen radicals, which inactivate NEP.(ABSTRACT TRUNCATED AT 250 WORDS)
Heparin prevents antigen-induced airway hyperresponsiveness: interference with IP3-mediated mast cell degranulation?
Authors: Ahmed T. , Syriste T. , Mendelssohn R. , Sorace D. , Mansour E. , Lansing M. , Abraham W. M. , Robinson M. J.
Published: December 2017

We hypothesized that heparin, because of its antiallergic and/or anti-inflammatory properties, modifies airway hyperresponsiveness (AHR). We studied the effects of inhaled heparin on AHR induced by specific antigen or by platelet-activating factor (PAF), a proinflammatory mediator. Specific lung resistance (sRL) was measured in 17 allergic sheep before, immediately after, and serially for up to 2 h after airway challenge with either specific antigen or PAF. Airway responsiveness was expressed as the cumulative provocative dose of carbachol that increased sRL to 4 cmH2O/s [PD4, in breath units (BU; 1 BU = 1 breath of 1% carbachol solution)]. PD4 was determined on a baseline day and on various experimental days 2 h after airway challenge with antigen or PAF, without or after pretreatment with inhaled heparin (1,000 U/kg). Pretreatment with inhaled heparin prevented antigen-induced bronchoconstriction and postantigen AHR. PD4 was 26 +/- 2.6 (SE), 12 +/- 1.7, and 22 +/- 2.8 BU on baseline, antigen control, and postheparin days, respectively. Heparin given immediately after the antigen challenge failed to modify the magnitude and/or duration of antigen-induced bronchoconstrictor response or postantigen AHR. Heparin also failed to prevent PAF-induced changes in sRL and AHR. In vitro heparin inhibited anti-immunoglobin E- and 1,4,5-inositol triphosphate-mediated degranulation of rat peritoneal mast cells without attenuating the effects of the Ca2+ ionophore A-23187. These data suggest that in “acute responders” heparin prevents antigen-induced bronchoconstriction and AHR, possibly by inhibiting 1,4,5-inositol triphosphate-dependent mast cell mediator release and not by its anti-inflammatory action.
Proton-Gated Channels in PC12 Cells
Authors: Chu Xiang-Ping , Miesch Jennifer , Johnson Martha , Root Leslie , Zhu Xiao-Man , Chen Dexi , Simon Roger P. , Xiong Zhi-Gang
Published: December 2017

Acid-sensing ion channels (ASICs) are expressed in various sensory and central neurons. The functional role of these channels remains elusive. Complex subunit combinations and lack of specific blockers for native receptors are likely to contribute to the difficulty of resolving the function of ASICs. Finding a neuronal cell line, which expresses a single population of ASICs, should prove to be useful in delineating the function of individual ASICs. Using patch-clamp, Ca2+-imaging, and RT-PCR techniques, we have explored the existence of ASICs in PC12 cells, a clonal neuronal cell line. Fast drops of extracellular pH activated transient inward currents in PC12 cells with pH0.5at 6.0–6.2. The ASICs in PC12 cells were selective for Na+with significant Ca2+permeability. Currents in PC12 cells were blocked by the nonselective ASIC blocker amiloride. PcTX1, a specific homomeric ASIC1a blocker, also blocked the ASIC currents with an IC50of ∼1.5 nM. RT-PCR demonstrated the existence of ASIC1a transcript in both undifferentiated and nerve growth factor–differentiated PC12 cells. Our data suggest that PC12 cells likely contain a single population of functional proton-gated channel–homomeric ASIC1a. It might be an ideal neuronal cell line for the study of physiological and potential pathological roles of this key subunit of ASICs.
Experimental Spinal Cord Injury: Spatiotemporal Characterization of Elemental Concentrations and Water Contents in Axons and Neuroglia
Authors: LoPachin Richard M. , Gaughan Christopher L. , Lehning Ellen J. , Kaneko Yoshiro , Kelly Thomas M. , Blight Andrew
Published: December 2017

To examine the role of axonal ion deregulation in acute spinal cord injury (SCI), white matter strips from guinea pig spinal cord were incubated in vitro and were subjected to graded focal compression injury. At several postinjury times, spinal segments were removed from incubation and rapidly frozen. X-ray microanalysis was used to measure percent water and dry weight elemental concentrations (mmol/kg) of Na, P, Cl, K, Ca, and Mg in selected morphological compartments of myelinated axons and neuroglia from spinal cord cryosections. As an index of axon function, compound action potentials (CAP) were measured before compression and at several times thereafter. Axons and mitochondria in epicenter of severely compressed spinal segments exhibited early (5 min) increases in mean Na and decreases in K and Mg concentrations. These elemental changes were correlated to a significant reduction in CAP amplitude. At later postcompression times (15 and 60 min), elemental changes progressed and were accompanied by alterations in compartmental water content and increases in mean Ca. Swollen axons were evident at all postinjury times and were characterized by marked element and water deregulation. Neuroglia and myelin in severely injured epicenter also exhibited significant disruptions. In shoulder areas (adjacent to epicenter) of severely injured spinal strips, axons and mitochondria exhibited modest increases in mean Na in conjunction with decreases in K, Mg, and water content. Following moderate compression injury to spinal strips, epicenter axons exhibited early (10 min postinjury) element and water deregulation that eventually recovered to near control values (60 min postinjury). Na+ channel blockade by tetrodotoxin (TTX, 1 μM) perfusion initiated 5 min after severe crush diminished both K loss and the accumulation of Na, Cl, and Ca in epicenter axons and neuroglia, whereas in shoulder regions TTX perfusion completely prevented subcellular elemental deregulation. TTX perfusion also reduced Na entry in swollen axons but did not affect K loss or Ca gain. Thus graded compression injury of spinal cord produced subcellular elemental deregulation in axons and neuroglia that correlated with the onset of impaired electrophysiological function and neuropathological alterations. This suggests that the mechanism of acute SCI-induced structural and functional deficits are mediated by disruption of subcellular ion distribution. The ability of TTX to reduce elemental deregulation in compression-injured axons and neuroglia implicates a significant pathophysiological role for Na+ influx in SCI and suggests Na+ channel blockade as a pharmacotherapeutic strategy.
Effects of GABA Receptor Antagonist on Trigeminal Caudalis Nociceptive Neurons in Normal and Neonatally Capsaicin-Treated Rats
Authors: Chiang Chen Yu , Kwan Chun L. , Hu James W. , Sessle Barry J.
Published: December 2017

We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-d-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABAA receptor antagonist bicuculline (BIC) or the GABAB receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABAA receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABAA receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABABreceptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABAA receptor–mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABAAreceptor–mediated modulation may be disrupted such that a GABAA receptor–mediated excitation is manifested.
Control of Grasp Stability in Humans Under Different Frictional Conditions During Multidigit Manipulation
Authors: Burstedt Magnus K. O. , Flanagan J. Randall , Johansson Roland S.
Published: December 2017

Control of grasp stability under different frictional conditions has primarily been studied in manipulatory tasks involving two digits only. Recently we found that many of the principles for control of forces originally demonstrated for two-digit grasping also apply to various three-digit grasps. Here we examine the control of grasp stability in a multidigit task in which subjects used the tips of the thumb, index, and middle finger to lift an object. The grasp resembled those used when lifting a cylindrical object from above. The digits either all contacted the same surface material or one of the digits contacted a surface material that was more, or less, slippery than that contacted by the other two digits. The three-dimensional forces and torques applied by each digit and the contact positions were measured along with the position and orientation of the object. The distribution of forces among the digits strongly reflected constraints imposed by the geometric relationship between the object's center of mass and the contact surfaces. On top of this distribution, we observed changes in force coordination related to changes in the combination of surface materials. When all digits contacted the same surface material, the ratio between the normal force and tangential load ( F n: L ratio) was similar across digits and scaled to provide an adequate safety margin against slip. With different contact surfaces subjects adapted the F n: L ratios at the individual digits to the local friction with only small influences by the friction at the other two digits. They accomplished this by scaling the normal forces similarly at all digits and changing the distribution of load among the digits. The surface combination did not, however, influence digit position, tangential torque, or object tilting systematically. The change in load distribution, rather, resulted from interplay between these factors, and the nature of this interplay varied between trials. That is, subjects achieved grasp stability with various combinations of fingertip actions and appeared to exploit the many degrees of freedom offered by the multidigit grasp. The results extend previous findings based on two-digit tasks to multidigit tasks by showing that subjects adjust fingertip forces at each digit to the local friction. Moreover, our findings suggest that subjects adapted the load distribution to the current frictional condition by regulating the normal forces to allow slips to occur early in the lift task, prior to object lift-off.
Carbachol Induces Fast Oscillations in the Medial but not in the Lateral Entorhinal Cortex of the Isolated Guinea Pig Brain
Authors: van der Linden Solange , Panzica Ferruccio , de Curtis Marco
Published: December 2017

Fast oscillations at 25–80 Hz (gamma activity) have been proposed to play a role in attention-related mechanisms and synaptic plasticity in cortical structures. Recently, it has been demonstrated that the preservation of the entorhinal cortex is necessary to maintain gamma oscillations in the hippocampus. Because gamma activity can be reproduced in vitro by cholinergic activation, this study examined the characteristics of gamma oscillations induced by arterial perfusion or local intracortical injections of carbachol in the entorhinal cortex of the in vitro isolated guinea pig brain preparation. Shortly after carbachol administration, fast oscillatory activity at 25.2–28.2 Hz was observed in the medial but not in the lateral entorhinal cortex. Such activity was transiently associated with oscillations in the theta range that showed a variable pattern of distribution in the entorhinal cortex. No oscillatory activity was observed when carbachol was injected in the lateral entorhinal cortex. Gamma activity in the medial entorhinal cortex showed a phase reversal at 200–400 μm, had maximal amplitude at 400–500 μm depth, and was abolished by arterial perfusion of atropine (5 μM). Local carbachol application in the medial entorhinal cortex induced gamma oscillations in the hippocampus, whereas no oscillations were observed in the amygdala and in the piriform, periamygdaloid, and perirhinal cortices ipsilateral and contralateral to the carbachol injection. Hippocampal oscillations had higher frequency than the gamma activity recorded in the entorhinal cortex, suggesting the presence of independent generators in the two structures. The selective ability of the medial but not the lateral entorhinal cortex to generate gamma activity in response to cholinergic activation suggests a differential mode of signal processing in entorhinal cortex subregions.
Auditory Spatial Discriminatory and Mnemonic Neurons in Rat Posterior Parietal Cortex
Authors: Nakamura Kiyomi
Published: December 2017

The present study was designed to investigate whether the rat posterior parietal cortex is involved in the perception and the representation of the auditory space. We recorded single neural activity in the posterior parietal cortex of rats that performed a directional delayed nonmatching-to-sample task. In the task, cue tones were presented in one of six speakers that were placed symmetrically around the rats. “Familiar tones” were those repeatedly used in the course of behavioral training. Novel tones were presented only during the unit recording time and less frequently used (e.g., only once in alternate weeks). The responses of the posterior parietal cortex neurons were typically tested with familiar cue tones while the rats were situated in a particular geomagnetic orientation. The same cells were further tested while the rats were reoriented by 180°, or by novel cue tones. As the task included a delay period, in which the cue tone was removed, the rats had to maintain the directional information of the cue tones during this period to maximize the reward rates. A well-trained rat could perform the task with 85% success. We found two major types of neurons intermixed in the rat posterior parietal cortex. One type ( n = 14) mainly discriminated the direction of the cue tones, whereas the other ( n = 36) carried a mnemonic value of the cue tones while the tones were removed. The former responded only during the cue tone period (discriminatory neurons), whereas the latter responded during the cue tone period and the delay period (mnemonic neurons). These cells also exhibited broad directional tuning. The results agreed with previous studies, suggesting that a population coding scheme exists in the posterior parietal cortex. When the cells were tested with novel tones or when the rats were rotated through 180°, the vast majority of the cells exhibited a directional tuning similar to those under the control conditions. Three quarters (18/24) of the cells that exhibited a mnemonic characteristic persisted in their directional preference when the rat's orientation was changed (12/17 neurons) or when an unfamiliar auditory stimulus was used (6/7 neurons). Half of the discriminatory neurons (4/8 neurons) persisted in their directional preference. These results, consistent with previous behavioral studies, suggest an allocentric representation of the auditory processing in this area. Furthermore, when the rat was reoriented or an unfamiliar cue tone was used, both the average and peak directional responses were enhanced in more than half of the mnemonic or discriminatory neurons. These results support the frequency-dependent neocortical gating hypothesis of the entorhinal hippocampal loop.
Paradoxical Effect of QX-314 on Persistent Inward Currents and Bistable Behavior in Spinal Motoneurons In Vivo
Authors: Lee R. H. , Heckman C. J.
Published: December 2017

Spinal motoneurons can exhibit bistable behavior, which consists of stable self-sustained firing that is initiated by a brief excitatory input and terminated by brief inhibitory input. This bistable behavior is generated by a persistent inward current ( I PIC). In cat motoneurons with low input conductances and slow axonal conduction velocities, I PIC exhibits little decay with time and thus self-sustained firing is long-lasting. In contrast, in cells that have high input conductances and fast conduction velocities, I PIC decays with time, and these cells cannot maintain long duration self-sustained firing. An alternative way to measure bistable behavior is to assess plateau potentials after the action potential has been blocked by intracellular injection of QX-314 to block sodium (Na+) currents. However, QX-314 also blocks calcium (Ca2+) currents and, because I PIC may be generated by a mixture of Ca2+ and Na+ currents, a reduction in amplitude of I PIC was expected. We therefore systematically compared the properties of I PIC in a sample of cells recorded with QX-314 to a control sample of cells without QX-314, which was obtained in a previous study. Single-electrode voltage-clamp techniques were applied in spinal motoneurons in the decerebrate cat preparation following administration of a standardized dose of the noradrenergic α1 agonist methoxamine. In the sample with QX-314, the average value of I PIC was only about half that in the control sample. However, the reduction of I PIC was much greater in cells with slow as compared with fast conduction velocities. Because a substantial portion of I PIC originates in dendritic regions and because conduction velocity covaries with the extent of the dendritic tree, this result suggests that QX-314 may fail to diffuse very far into the dendrites of the largest motoneurons. The analysis of the decay of I PIC and plateau potentials in cells with QX-314 also produced an unexpected result: QX-314 virtually eliminated time-dependent decay in both I PICand plateau potentials. Consequently, I PICbecame equally persistent in high and low input conductance cells. Therefore the decay in I PIC in high input conductance cells in the absence of QX-314 is not due to an intrinsic tendency of the underlying inward current to decay. Instead it is possible that the decay may result from activation of a slow outward current. Overall, these results show that QX-314 has a profound effect on I PIC and thus plateau potentials obtained using QX-314 do not accurately reflect the properties of I PIC in normal cells without QX-314.
Frequency Organization and Responses to Complex Sounds in the Medial Geniculate Body of the Mustached Bat
Authors: Wenstrup Jeffrey J.
Published: December 2017

The auditory cortex of the mustached bat ( Pteronotus parnellii) displays some of the most highly developed physiological and organizational features described in mammalian auditory cortex. This study examines response properties and organization in the medial geniculate body (MGB) that may contribute to these features of auditory cortex. About 25% of 427 auditory responses had simple frequency tuning with single excitatory tuning curves. The remainder displayed more complex frequency tuning using two-tone or noise stimuli. Most of these were combination-sensitive, responsive to combinations of different frequency bands within sonar or social vocalizations. They included FM-FM neurons, responsive to different harmonic elements of the frequency modulated (FM) sweep in the sonar signal, and H1-CF neurons, responsive to combinations of the bat's first sonar harmonic (H1) and a higher harmonic of the constant frequency (CF) sonar signal. Most combination-sensitive neurons (86%) showed facilitatory interactions. Neurons tuned to frequencies outside the biosonar range also displayed combination-sensitive responses, perhaps related to analyses of social vocalizations. Complex spectral responses were distributed throughout dorsal and ventral divisions of the MGB, forming a major feature of this bat's analysis of complex sounds. The auditory sector of the thalamic reticular nucleus also was dominated by complex spectral responses to sounds. The ventral division was organized tonotopically, based on best frequencies of singly tuned neurons and higher best frequencies of combination-sensitive neurons. Best frequencies were lowest ventrolaterally, increasing dorsally and then ventromedially. However, representations of frequencies associated with higher harmonics of the FM sonar signal were reduced greatly. Frequency organization in the dorsal division was not tonotopic; within the middle one-third of MGB, combination-sensitive responses to second and third harmonic CF sonar signals (60–63 and 90–94 kHz) occurred in adjacent regions. In the rostral one-third, combination-sensitive responses to second, third, and fourth harmonic FM frequency bands predominated. These FM-FM neurons, thought to be selective for delay between an emitted pulse and echo, showed some organization of delay selectivity. The organization of frequency sensitivity in the MGB suggests a major rewiring of the output of the central nucleus of the inferior colliculus, by which collicular neurons tuned to the bat's FM sonar signals mostly project to the dorsal, not the ventral, division. Because physiological differences between collicular and MGB neurons are minor, a major role of the tecto-thalamic projection in the mustached bat may be the reorganization of responses to provide for cortical representations of sonar target features.
IP3-Independent Release of Ca2+From Intracellular Stores: A Novel Mechanism for Transduction of Bitter Stimuli
Authors: Ogura Tatsuya , Kinnamon Sue C.
Published: December 2017

A variety of substances with different chemical structures elicits a bitter taste. Several different transduction mechanisms underlie detection of bitter tastants; however, these have been described in detail for only a few compounds. In addition, most studies have focused on mammalian taste cells, of which only a small subset is responsive to any particular bitter compound. In contrast, ∼80% of the taste cells in the mudpuppy, Necturus maculosus, are bitter-responsive. In this study, we used Ca2+imaging and giga-seal whole cell recording to compare the transduction of dextromethorphan (DEX), a bitter antitussive, with transduction of the well-studied bitter compound denatonium. Bath perfusion of DEX (2.5 mM) increased the intracellular Ca2+level in most taste cells. The DEX-induced Ca2+increase was inhibited by thapsigargin, an inhibitor of Ca2+transport into intracellular stores, but not by U73122, an inhibitor of phospholipase C, or by ryanodine, an inhibitor of ryanodine-sensitive Ca2+stores. Increasing intracellular cAMP levels with a cell-permeant cAMP analogue and a phosphodiesterase inhibitor enhanced the DEX-induced Ca2+increase, which was inhibited partially by H89, a protein kinase A inhibitor. Electrophysiological measurements showed that DEX depolarized the membrane potential and inhibited voltage-gated Na+and K+currents in the presence of GDP-β-S, a blocker of G-protein activation. DEX also inhibited voltage-gated Ca2+channels. We suggest that DEX, like quinine, depolarizes taste cells by block of voltage-gated K channels, which are localized to the apical membrane in mudpuppy. In addition, DEX causes release of Ca2+from intracellular stores by a phospholipase C-independent mechanism. We speculate that the membrane-permeant DEX may enter taste cells and interact directly with Ca2+stores. Comparing transduction of DEX with that of denatonium, both compounds release Ca2+from intracellular stores. However, denatonium requires activation of phospholipase C, and the mechanism results in a hyperpolarization rather than a depolarization of the membrane potential. These data support the hypothesis that single taste receptor cells can use multiple mechanisms for transducing the same bitter compound.
Evidence for Involvement of Group II/III Metabotropic Glutamate Receptors in NMDA Receptor–Independent Long-Term Potentiation in Area CA1 of Rat Hippocampus
Authors: Grover Lawrence M. , Yan Chen
Published: December 2017

Previous studies implicated metabotropic glutamate receptors (mGluRs) in N-methyl-d-aspartate (NMDA) receptor–independent long-term potentiation (LTP) in area CA1 of the rat hippocampus. To learn more about the specific roles played by mGluRs in NMDA receptor–independent LTP, we used whole cell recordings to load individual CA1 pyramidal neurons with a G-protein inhibitor [guanosine-5′-O-(2-thiodiphosphate), GDPβS]. Although loading postsynaptic CA1 pyramidal neurons with GDPβS significantly reduced G-protein dependent postsynaptic potentials, GDPβS failed to prevent NMDA receptor– independent LTP, suggesting that postsynaptic G-protein–dependent mGluRs are not required. We also performed a series of extracellular field potential experiments in which we applied group-selective mGluR antagonists. We had previously determined that paired-pulse facilitation (PPF) was decreased during the first 30–45 min of NMDA receptor–independent LTP. To determine if mGluRs might be involved in these PPF changes, we used a twin-pulse stimulation protocol to measure PPF in field potential experiments. NMDA receptor–independent LTP was prevented by a group II mGluR antagonist [(2S)-α-ethylglutamic acid] and a group III mGluR antagonist [(RS)-α-cyclopropyl-4-phosphonophenylglycine], but was not prevented by other group II and III mGluR antagonists [(RS)-α-methylserine-O-phosphate monophenyl ester or (RS)-α-methylserine-O-phosphate]. NMDA receptor–independent LTP was not prevented by either of the group I mGluR antagonists we examined, (RS)-1-aminoindan-1,5-dicarboxylic acid and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. The PPF changes which accompany NMDA receptor–independent LTP were not prevented by any of the group-selective mGluR antagonists we examined, even when the LTP itself was blocked. Finally, we found that tetanic stimulation in the presence of group III mGluR antagonists lead to nonspecific potentiation in control (nontetanized) input pathways. Taken together, our results argue against the involvement of postsynaptic group I mGluRs in NMDA receptor–independent LTP. Group II and/or group III mGluRs are required, but the specific details of the roles played by these mGluRs in NMDA receptor–independent LTP are uncertain. Based on the pattern of results we obtained, we suggest that group II mGluRs are required for induction of NMDA receptor–independent LTP, and that group III mGluRs are involved in determining the input specificity of NMDA receptor–independent LTP by suppressing potentiation of nearby, nontetanized synapses.
Coordinated Ground Forces Exerted by Buttocks and Feet are Adequately Programmed for Weight Transfer During Sit-to-Stand
Authors: Hirschfeld Helga , Thorsteinsdottir Maria , Olsson Elisabeth
Published: December 2017

The purpose of this study was to test the hypothesis whether weight transfer during sit-to-stand (STS) is the result of coordinated ground forces exerted by buttocks and feet before seat-off. Whole-body kinematics and three-dimensional ground forces from left and right buttock as well as from left and right foot were recorded for seven adults during STS. We defined a preparatory phase from onset of the first detectable anterior/posterior (A/P) force to seat-off (buttock forces fell to 0) and a rising phase from seat-off to the decrease of center of mass (CoM) vertical velocity to zero. STS was induced by an increase of vertical and backward directed ground forces exerted by the buttocks that significantly preceded the onset of any trunk movement. All ground forces peaked before or around the moment of seat-off, whereas all kinematic variables, except trunk forward rotation and hip flexion, peaked after seat-off, during or after the rising phase. The present study suggests that the weight transfer from sit to stand is induced by ground forces exerted by buttocks and feet before seat-off, i.e., during the preparatory phase. The buttocks generate the isometric “rising forces,” e.g., the propulsive impulse for the forward acceleration of the body, while the feet apply adequate damping control before seat-off. This indicates that the rising movement is a result of these coordinated forces, targeted to match the subject's weight and support base distance between buttocks and feet. The single peaked, bell-shaped profiles peaking before seat-off, were seen beneath buttocks for the “rising drive,” i.e., between the time of peak backward directed force and seat-off, as well as beneath the feet for the “damping drive,” i.e., from onset to the peak of forward-directed force and for CoM A/P velocity. This suggests that both beginning and end of the weight transfer process are programmed before seat-off. The peak deceleration of A/P CoM took place shortly (∼100 ms) after CoM peak velocity, resulting in a well controlled CoM deceleration before seat-off. In contrast to the view of other authors, this suggests that body equilibrium is controlled during weight transfer.