bluuebunny/crossref_metadata_2025 huggingface dataset:
Models of Respiratory Rhythm Generation in the Pre-Bötzinger Complex. II. Populations of Coupled Pacemaker Neurons
Authors: Butera Robert J. , Rinzel John , Smith Jeffrey C.
Published: December 2017

We have proposed models for the ionic basis of oscillatory bursting of respiratory pacemaker neurons in the pre-Bötzinger complex. In this paper, we investigate the frequency control and synchronization of these model neurons when coupled by excitatory amino-acid-mediated synapses and controlled by convergent synaptic inputs modeled as tonic excitation. Simulations of pairs of identical cells reveal that increasing tonic excitation increases the frequency of synchronous bursting, while increasing the strength of excitatory coupling between the neurons decreases the frequency of synchronous bursting. Low levels of coupling extend the range of values of tonic excitation where synchronous bursting is found. Simulations of a heterogeneous population of 50–500 bursting neurons reveal coupling effects similar to those found experimentally in vitro: coupling increases the mean burst duration and decreases the mean burst frequency. Burst synchronization occurred over a wide range of intrinsic frequencies (0.1–1 Hz) and even in populations where as few as 10% of the cells were intrinsically bursting. Weak coupling, extreme parameter heterogeneity, and low levels of depolarizing input could contribute to the desynchronization of the population and give rise to quasiperiodic states. The introduction of sparse coupling did not affect the burst synchrony, although it did make the interburst intervals more irregular from cycle to cycle. At a population level, both parameter heterogeneity and excitatory coupling synergistically combine to increase the dynamic input range: robust synchronous bursting persisted across a much greater range of parameter space (in terms of mean depolarizing input) than that of a single model cell. This extended dynamic range for the bursting cell population indicates that cellular heterogeneity is functionally advantageous. Our modeled system accounts for the range of intrinsic frequencies and spiking patterns of inspiratory (I) bursting cells found in the pre-Bötzinger complex in neonatal rat brain stem slices in vitro. There is a temporal dispersion in the spiking onset times of neurons in the population, predicted to be due to heterogeneity in intrinsic neuronal properties, with neurons starting to spike before (pre-I), with (I), or after (late-I) the onset of the population burst. Experimental tests for a number of the model’s predictions are proposed.
Integration of Vestibular and Head Movement Signals in the Vestibular Nuclei During Whole-Body Rotation
Authors: Gdowski Greg T. , McCrea Robert A.
Published: December 2017

Single-unit recordings were obtained from 107 horizontal semicircular canal-related central vestibular neurons in three alert squirrel monkeys during passive sinusoidal whole-body rotation (WBR) while the head was free to move in the yaw plane (2.3 Hz, 20°/s). Most of the units were identified as secondary vestibular neurons by electrical stimulation of the ipsilateral vestibular nerve (61/80 tested). Both non–eye-movement ( n = 52) and eye-movement–related ( n = 55) units were studied. Unit responses recorded when the head was free to move were compared with responses recorded when the head was restrained from moving. WBR in the absence of a visual target evoked a compensatory vestibulocollic reflex (VCR) that effectively reduced the head velocity in space by an average of 33 ± 14%. In 73 units, the compensatory head movements were sufficiently large to permit the effect of the VCR on vestibular signal processing to be assessed quantitatively. The VCR affected the rotational responses of different vestibular neurons in different ways. Approximately one-half of the units (34/73, 47%) had responses that decreased as head velocity decreased. However, the responses of many other units (24/73) showed little change. These cells had signals that were better correlated with trunk velocity than with head velocity. The remaining units had responses that were significantly larger (15/73, 21%) when the VCR produced a decrease in head velocity. Eye-movement–related units tended to have rotational responses that were correlated with head velocity. On the other hand, non–eye-movement units tended to have rotational responses that were better correlated with trunk velocity. We conclude that sensory vestibular signals are transformed from head-in-space coordinates to trunk-in-space coordinates on many secondary vestibular neurons in the vestibular nuclei by the addition of inputs related to head rotation on the trunk. This coordinate transformation is presumably important for controlling postural reflexes and constructing a central percept of body orientation and movement in space.
Functional Anatomy of Pursuit Eye Movements in Humans as Revealed by fMRI
Authors: Petit Laurent , Haxby James V.
Published: December 2017

We have investigated the functional anatomy of pursuit eye movements in humans with functional magnetic imaging. The performance of pursuit eye movements induced activations in the cortical eye fields also activated during the execution of visually guided saccadic eye movements, namely in the precentral cortex [frontal eye field (FEF)], the medial superior frontal cortex (supplementary eye field), the intraparietal cortex (parietal eye field), and the precuneus, and at the junction of occipital and temporal cortex (MT/MST) cortex. Pursuit-related areas could be distinguished from saccade-related areas both in terms of spatial extent and location. Pursuit-related areas were smaller than their saccade-related counterparts, three of eight significantly so. The pursuit-related FEF was usually inferior to saccade-related FEF. Other pursuit-related areas were consistently posterior to their saccade-related counterparts. The current findings provide the first functional imaging evidence for a distinction between two parallel cortical systems that subserve pursuit and saccadic eye movements in humans.
NPY Inhibits Glutamatergic Excitation in the Epileptic Human Dentate Gyrus
Authors: Patrylo Peter R. , van den Pol Anthony N. , Spencer Dennis D. , Williamson Anne
Published: December 2017

Neuropeptide Y (NPY) has been shown to depress hyperexcitable activity that has been acutely induced in the normal rat brain. To test the hypothesis that NPY can also reduce excitability in the chronically epileptic human brain, we recorded intracellularly from dentate granule cells in hippocampal slices from patients with hippocampal seizure onset. NPY had a potent and long-lasting inhibitory action on perforant path-evoked excitatory responses. In comparison, the group 3 metabotropic glutamate receptor agonistl-2-amino-4-phosphonobutyric acid (l-AP4) evoked a mild and transient decrease. NPY-containing axons were found throughout the hippocampus, and in many epileptic patients were reorganized, particularly in the dentate molecular layer. NPY may therefore play a beneficial role in reducing granule cell excitability in chronically epileptic human tissue, and subsequently limit seizure severity.
Protein Synthesis–Dependent and mRNA Synthesis–Independent Intermediate Phase of Memory in Hermissenda
Authors: Crow Terry , Xue-Bian Juan-Juan , Siddiqi Vilma
Published: December 2017

The conditioned stimulus pathway in Hermissenda has been used to examine the time-dependent mechanisms of memory consolidation following one-trial conditioning. Here we report an intermediate phase of memory consolidation following one-trial conditioning that requires protein synthesis, but not mRNA synthesis. In conditioned animals, enhanced excitability normally expressed during an intermediate phase of memory was reversed by the protein synthesis inhibitor anisomycin, but not by the mRNA synthesis inhibitor 5,6-dichloro-1-β-d-ribobenzimidazole (DRB). Associated with the intermediate phase of memory is an increase in the phosphorylation of a 24-kDa protein. Anisomycin present during the intermediate phase blocked the increased phosphorylation of the 24-kDa phosphoprotein, but did not block the increased phosphorylation of other proteins associated with conditioning or significantly change their baseline phosphorylation. DRB did not reverse enhanced excitability or decrease protein phosphorylation expressed during the intermediate phase of memory formation, but it did reverse enhanced excitability 3.5 h after conditioning. Phosphorylation of the 24-kDa protein may support enhanced excitability during the intermediate phase, in the transition period between short- and long-term memory.
Muscle Spindle Afferent Input to Motoneurons in Human Masseter
Authors: Scutter Sheila D. , Türker Kemal S.
Published: December 2017

The H-reflex response in large and small single motor units in human deep anterior masseter was studied to investigate the distribution of muscle spindle afferents onto masseter motoneurons. We found that only the larger units displayed H-reflex responses. This indicates preferential distribution of muscle spindle input onto large motoneurons or a skewed distribution of tonic presynaptic inhibitory mechanisms.
Effect of the Group II Metabotropic Glutamate Agonist, 2R,4R-APDC, Varies With Age, Layer, and Visual Experience in the Visual Cortex
Authors: Beaver C. J. , Ji Q.-H. , Daw N. W.
Published: December 2017

Group II metabotropic glutamate receptors (mGluR 2/3) are distributed differentially across the layers of cat visual cortex, and this distribution varies with age. At 3–4 wk, mGluR 2/3 receptor immunoreactivity is present in all layers. By 6–8 wk of age, it is still present in extragranular layers (2, 3, 5, and 6) but has disappeared from layer 4, and dark-rearing postpones the disappearance of Group II receptors from layer 4. We examined the physiological effects of Group II activation, to see if these effects varied similarly. The responses of single neurons in cat primary visual cortex were recorded to visual stimulation, then the effect of iontophoresis of 2R,4R-4 aminopyrrolidine-2,4-decarboxylate (2R,4R-APDC), a Group II specific agonist, was observed in animals between 3 wk and adulthood. The effect of 2R,4R-APDC was generally suppressive, reducing both the visual response and spontaneous activity of single neurons. The developmental changes were in agreement with the immunohistochemical results: 2R,4R-APDC had effects on cells in all layers in animals of 3–4 wk but not in layer 4 of animals >6 wk old. Moreover, the effect of 2R,4R-APDC was reduced in the cortex of older animals (>22 wk). Dark-rearing animals to 47–54 days maintained the effects of 2R,4R-APDC in layer 4. The disappearance of Group II mGluRs from layer 4 between 3 and 6 wk of age is correlated with the segregation of ocular dominance columns in that layer, raising the possibility that mGluRs 2/3 are involved in this process.
Proprioceptive and Retinal Afference Modify Postsaccadic Ocular Drift
Authors: Lewis Richard F. , Zee David S. , Goldstein Herschel P. , Guthrie Barton L.
Published: December 2017

Drift of the eyes after saccades produces motion of images on the retina (retinal slip) that degrades visual acuity. In this study, we examined the contributions of proprioceptive and retinal afference to the suppression of postsaccadic drift induced by a unilateral ocular muscle paresis. Eye movements were recorded in three rhesus monkeys with a unilateral weakness of one vertical extraocular muscle before and after proprioceptive deafferentation of the paretic eye. Postsaccadic drift was examined in four visual states: monocular viewing with the normal eye (4-wk period); binocular viewing (2-wk period); binocular viewing with a disparity-reducing prism (2-wk period); and monocular viewing with the paretic eye (2-wk period). The muscle paresis produced vertical postsaccadic drift in the paretic eye, and this drift was suppressed in the binocular viewing condition even when the animals could not fuse. When the animals viewed binocularly with a disparity-reducing prism, the drift in the paretic eye was suppressed in two monkeys (with superior oblique pareses) but generally was enhanced in one animal (with a tenotomy of the inferior rectus). When drift movements were enhanced, they reduced the retinal disparity that was present at the end of the saccade. In the paretic-eye–viewing condition, postsaccadic drift was suppressed in the paretic eye and was induced in the normal eye. After deafferentation in the normal-eye–viewing state, there was a change in the vertical postsaccadic drift of the paretic eye. This change in drift was idiosyncratic and variably affected the amplitude and velocity of the postsaccadic drift movements of the paretic eye. Deafferentation of the paretic eye did not affect the postsaccadic drift of the normal eye nor did it impair visually mediated adaptation of postsaccadic drift. The results demonstrate several new findings concerning the roles of visual and proprioceptive afference in the control of postsaccadic drift: disconjugate adaptation of postsaccadic drift does not require binocular fusion; slow, postsaccadic drift movements that reduce retinal disparity but concurrently increase retinal slip can be induced in the binocular viewing state; postsaccadic drift is modified by proprioception from the extraocular muscles, but these modifications do not serve to minimize retinal slip or to correct errors in saccade amplitude; and visually mediated adaptation of postsaccadic drift does not require proprioceptive afference from the paretic eye.
Micromechanical Responses to Tones in the Auditory Fovea of the Greater Mustached Bat’s Cochlea
Authors: Russell I. J. , Kössl M.
Published: December 2017

An extended region of the greater mustached bat’s cochlea, the sparsely innervated (SI) zone, is located just basally to the frequency place of the dominant 61-kHz component of the echolocation signal (CF2). Anatomic adaptations in the SI zone are thought to provide the basis for cochlear resonance to the CF2 echoes and for the extremely sharp tuning throughout the auditory system that allows these bats to detect Doppler shifts in the echoes caused by insect wing beat. We measured basilar membrane (BM) displacements in the SI zone with a laser interferometer and recorded acoustic distortion products at the ear drum at frequencies represented in the SI zone. The basilar membrane in the SI region was tuned both to its characteristic frequency (62–72 kHz) and to the resonance frequency (61–62 kHz). With increasing stimulus levels, the displacement growth functions are compressive curves with initial slopes close to unity, and their properties are consistent with the mammalian cochlear amplifier working at high sound frequencies. The sharp basilar membrane resonance is associated with a phase lag of 180° and with a shift of the peak resonance to lower frequencies for high stimulus levels. Within the range of the resonance, the distortion product otoacoustic emissions, which have been attributed to the resonance of the tectorial membrane in the SI region, are associated with an abrupt phase change of 360°. It is proposed that a standing wave resonance of the tectorial membrane drives the BM in the SI region and that the outer hair cells enhance, fine tune, and control the resonance. In the SI region, cochlear micromechanics appear to be able to work in two different modes: a conventional traveling wave leads to shear displacement between basilar and tectorial membrane and to neuronal excitation for 62–70 kHz. In addition, the SI region responds to 61–62 kHz with a resonance based on standing waves and thus preprocesses signals which are represented more apically in the CF2 region of the cochlea.
Neuronal Mechanisms for the Control of Body Orientation inClioneI. Spatial Zones of Activity of Different Neuron Groups
Authors: Deliagina T. G. , Orlovsky G. N. , Selverston A. I. , Arshavsky Y. I.
Published: December 2017

The marine mollusk Clione limacina,when swimming, can stabilize different body orientations in the gravitational field. Here we describe one of the modes of operation of the postural network in Clione—maintenance of the vertical, head-up orientation. Experiments were performed on the CNS-statocyst preparation. Spike discharges in the axons of different types of neurons were recorded extracellularly when the preparation was rotated in space through 360° in different planes. We characterized the spatial zones of activity of the tail and wing motor neurons as well as of the CPB3 interneurons mediating the effects of statocyst receptor cells on the tail motor neurons. It was found that the activity of the tail motor neurons increased with deviation of the preparation from the normal, rostral-side-up orientation. Their zones of activity were very wide (∼180°). According to the zone position, three distinct groups of tail motor neuron (T1–T3) could be distinguished. The T1 group had a center of the zone near the ventral-side-up orientation, whereas the zones of T2 and T3 had their centers near the left-side-up and the right-side-up positions, respectively. By comparing the zone of activity with the direction of tail bending elicited by each of the groups, one can conclude that gravitational reflexes mediated by the T1, T2, and T3 groups will evoke turning of the animal toward the head-up orientation. Two identified wing motor neurons, 1A and 2A, causing the wing beating, were involved in gravitational reactions. They were activated with the downward inclination of the ipsilateral side. Opposite reactions were observed in the motor neurons responsible for the wing retraction. A presumed motor effect of these reactions is an increase of oscillations in the wing that is directed downward and turning of Clionetoward the head-up orientation. Among the CPB3 interneurons, at least four groups could be distinguished. In three of them (IN1, IN2, and IN3), the zones of activity were similar to those of the three groups (T1, T2, and T3) of the tail motor neurons. The group IN4 had the center of its zone in the dorsal-side-up position; a corresponding group was not found among the tail motor neurons. In lesion experiments, it was found that gravitational input mediated by a single CPB3 interneuron produced activation of its target tail motor neurons in their normal zones, but the strength of response was reduced considerably. This finding suggests that several interneurons with similar spatial zones converge on individual tail motor neurons. In conclusion, because of a novel method, activity of the neuronal network responsible for the postural control in Clione was characterized in the terms of gravitational responses in different neuron groups comprising the network.
Activation Patterns of Hindlimb Motor Units in the Awake Rat and Their Relation to Motoneuron Intrinsic Properties
Authors: Gorassini Monica , Bennett David J. , Kiehn Ole , Eken Torsten , Hultborn Hans
Published: December 2017

The activity of hindlimb motor units from the lateral gastrocnemius and tibialis anterior muscles in the awake rat was compared during locomotion and during slow, sinusoidal muscle stretch. The majority of units were activated with high initial frequencies and often commenced firing with an initial doublet or triplet, even when activated by slow muscle stretch. The high firing rates at recruitment occurred without jumps in the firing rates of other concurrently activated units, the firing rate profiles of which were used as a measure of the net synaptic drive onto the motoneuronal pool. This suggested that the sharp recruitment jumps were not due to an abrupt increase in synaptic drive but rather due to intrinsic properties of the motoneuron. In addition, motor units that were activated phasically by the muscle stretch fired more action potentials during muscle shortening than during muscle lengthening, resulting in rightwardly skewed, asymmetrical firing profiles. In contrast, when the same units fired tonically during the imposed muscle stretch, the frequency profiles were modulated symmetrically and no nonlinearities were observed. Tonically firing units were modulated symmetrically throughout a wide range of firing frequencies, and discrete jumps in rate (i.e., bistable firing) were not observed. The sharp recruitment jumps during locomotion and muscle stretch are proposed to have resulted from the additional depolarization produced by the activation of plateau potentials at recruitment. Likewise, the sustained activation of plateaus subsequent to recruitment may have produced the prolonged firing of the motor units during sinusoidal muscle stretch.
VDCCs and NMDARs Underlie Two Forms of LTP in CA1 Hippocampus In Vivo
Authors: Morgan S. L. , Teyler T. J.
Published: December 2017

N-methyl-d-aspartate receptor/channel (NMDAR) and voltage-dependent calcium channel (VDCC) antagonists applied independently reduce the magnitude of long-term potentiation (LTP) in area CA1 of the hippocampal slice preparation. When used in combination, the antagonists completely block the induction of LTP. In urethan-anesthetized rats we examined the effect of the NMDAR blocker MK-801 (0.1 mg/kg) and the VDCC blocker Verapamil (10 mg/kg) on LTP induction in area CA1. Extracellular recordings were obtained from stratum radiatum following stimulation of Schaffer collaterals. LTP was induced by a 200-Hz/100-ms tetanus repeated 10 times (2 s isi). Tetanus was given in the presence of intraperitoneal saline, MK-801, Verapamil, or both Verapamil and MK-801. When given separately, Verapamil and MK-801 both significantly reduced the magnitude of LTP as compared with control animals. When given together, the drugs blocked the induction of LTP completely. We conclude that like LTP in vitro, VDCCs and NMDAR underlie two forms of LTP in vivo.
Neural Mechanisms for Encoding Binocular Disparity: Receptive Field Position Versus Phase
Authors: Anzai Akiyuki , Ohzawa Izumi , Freeman Ralph D.
Published: December 2017

The visual system uses binocular disparity to discriminate the relative depth of objects in space. Because the striate cortex is the first site along the central visual pathways at which signals from the left and right eyes converge onto a single neuron, encoding of binocular disparity is thought to begin in this region. There are two possible mechanisms for encoding binocular disparity through simple cells in the striate cortex: a difference in receptive field (RF) position between the two eyes (RF position disparity) and a difference in RF profiles between the two eyes (RF phase disparity). Although there is evidence that supports each of these schemes, both mechanisms have not been examined in a single study to determine their relative roles. In this study, we have measured RF position and phase disparities of individual simple cells in the cat’s striate cortex to address this issue. Using a sophisticated RF mapping technique that employs binary m-sequences, we have obtained left and right eye RF profiles of two or more cells recorded simultaneously. A version of the reference-cell method was used to estimate RF position disparity. We find that RF position disparities generally are limited to values that are not sufficient to encode large binocular disparities. In contrast, RF phase disparities cover a wide range of binocular disparities and exhibit dependencies on RF orientation and spatial frequency in a manner expected for a mechanism that encodes binocular disparity. These results suggest that binocular disparity is encoded mainly through RF phase disparity. However, RF position disparity may play a significant role for cells with high spatial frequency selectivity that are constrained to have only small RF phase disparities.
Ca2+-Dependent Inactivation of High-Threshold Ca2+ Currents in Hippocampal Granule Cells of Patients With Chronic Temporal Lobe Epilepsy
Authors: Beck Heinz , Steffens Ralf , Heinemann Uwe , Elger Christian E.
Published: December 2017

Intracellular Ca2+ represents an important trigger for various second-messenger mediated effects. Therefore a stringent control of the intracellular Ca2+ concentration is necessary to avoid excessive activation of Ca2+-dependent processes. Ca2+-dependent inactivation of voltage-dependent calcium currents (VCCs) represents an important negative feedback mechanism to limit the influx of Ca2+ that has been shown to be altered in the kindling model of epilepsy. We therefore investigated the Ca2+-dependent inactivation of high-threshold VCCs in dentate granule cells (DGCs) isolated from the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE) using the patch-clamp method. Ca2+ currents showed pronounced time-dependent inactivation when no extrinsic Ca2+ buffer was present in the patch pipette. In addition, in double-pulse experiments, Ca2+ entry during conditioning prepulses caused a reduction of VCC amplitudes elicited during a subsequent test pulse. Recovery from Ca2+-dependent inactivation was slow and only complete after 1 s. Ca2+-dependent inactivation could be blocked either by using Ba2+ as a charge carrier or by including bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) or EGTA in the intracellular solution. The influence of the cytoskeleton on Ca2+-dependent inactivation was investigated with agents that stabilize and destabilize microfilaments or microtubules, respectively. From these experiments, we conclude that Ca2+-dependent inactivation in human DGCs involves Ca2+-dependent destabilization of both microfilaments and microtubules. In addition, the microtubule-dependent pathway is modulated by the intracellular concentration of GTP, with lower concentrations of guanosine triphosphate (GTP) causing increased Ca2+-dependent inactivation. Under low-GTP conditions, the amount of Ca2+-dependent inactivation was similar to that observed in the kindling model. In summary, Ca2+-dependent inactivation was present in patients with TLE and Ammon’s horn sclerosis (AHS) and is mediated by the cytoskeleton similar to rat pyramidal neurons. The similarity to the kindling model of epilepsy may suggest the possibility of altered Ca2+-dependent inactivation in patients with AHS.
Model of the Control of Saccades by Superior Colliculus and Cerebellum
Authors: Quaia Christian , Lefèvre Philippe , Optican Lance M.
Published: December 2017

Experimental evidence indicates that the superior colliculus (SC) is important but neither necessary nor sufficient to produce accurate saccadic eye movements. Furthermore both clinical and experimental evidence points to the cerebellum as an indispensable component of the saccadic system. Accordingly, we have devised a new model of the saccadic system in which the characteristics of saccades are determined by the cooperation of two pathways, one through the SC and the other through the cerebellum. Both pathways are influenced by feedback information: the feedback determines the decay of activity for collicular neurons and the timing of the activation for cerebellar neurons. We have modeled three types of cells (burst, buildup, and fixation neurons) found in the intermediate layers of the superior colliculus. We propose that, from the point of view of motor execution, the burst neurons and the buildup neurons are not functionally distinct with both providing a directional drive to the brain stem circuitry. The fixation neurons determine the onset of the saccade by disfacilitating the omnipause neurons in the brain stem. Excluding noise-related variations, the ratio of the horizontal to the vertical components of the collicular drive is fixed throughout the saccade (i.e., its direction is fixed); the duration of the drive is such that it always would produce hypermetric movements. The cerebellum plays three roles: first, it provides an additional directional drive, which improves the acceleration of the eyes; second, it keeps track of the progress of the saccade toward the target; and third, it ends the saccade by choking off the collicular drive. The drive provided by the cerebellum can be adjusted in direction to exert a directional control over the saccadic trajectory. We propose here a control mechanism that incorporates a spatial displacement integrator in the cerebellum; under such conditions, we show that a partial directional control arises automatically. Our scheme preserves the advantages of several previous models of the saccadic system (e.g., the lack of a spatial-to-temporal transformation between the SC and the brain stem; the use of efference copy feedback to control the saccade), without incurring many of their drawbacks, and it accounts for a large amount of experimental data.
Discharge Patterns of Neurons in the Ventral Nucleus of the Lateral Lemniscus of the Unanesthetized Rabbit
Authors: Batra Ranjan , Fitzpatrick Douglas C.
Published: December 2017

The ventral nucleus of the lateral lemniscus (VNLL) is a major auditory nucleus that sends a large projection to the inferior colliculus. Despite its prominence, the responses of neurons in the VNLL have not been extensively studied. Previous studies in nonecholocating species have used anesthesia, which is known to affect discharge patterns. In addition, there is disagreement about the proportion of neurons that are sensitive to binaural stimulation. This report examines the responses of neurons in the VNLL of the unanesthetized rabbit to monaural and binaural stimuli. Most neurons responded to contralateral tone bursts at their best frequency and had either sustained or phasic discharge patterns. A few neurons were only inhibited. Most sustained neurons were classified as short-latency sustained (SL-sustained), but a few were of long latency. Some SL-sustained neurons exhibited multiple peaks in their discharge pattern, i.e., they had a “chopper” discharge pattern, whereas other SL-sustained neurons did not exhibit this pattern. In ordinary chopper neurons, the multiple peaks corresponded to the evenly spaced action potentials of a regular discharge. In unusual chopper neurons, the action potential associated with a particular peak could fail to occur during any one presentation of the stimulus. Unusual chopper neurons had a relatively irregular discharge. Phasic neurons were of two types: onset and transient. Onset neurons typically responded with a single action potential at the onset of the tone, whereas transient neurons produced a burst of action potentials. Transient neurons were relatively rare. About half the neurons also were influenced by ipsilateral stimulation. Most binaurally influenced neurons were either sensitive to interaural temporal disparities (ITDs) or excited by contralateral stimulation and inhibited by ipsilateral stimulation. Neurons sensitive to ITDs were mostly of the onset type and were embedded in the fiber tract medial to the main part of the nucleus. Neurons inhibited by ipsilateral stimulation could be of the sustained or onset type. The sustained neurons were located on the periphery of the main nucleus as well as in the fiber tract. Most of the monaural neurons were in the main, high-density part of VNLL. The present results demonstrate that the VNLL contains neurons with a heterogeneous set of responses, and that many of the neurons are binaural.
Vesicle-Associated Proteins and Quantal Release at Single Active Zones of Amphibian (Bufo marinus) Motor-Nerve Terminals
Authors: Macleod G. T. , Gan J.-B. , Bennett M. R.
Published: December 2017

A study was made to determine the disposition of vesicle-associated proteins (syntaxin, SV2, SNAP-25) and calcium channels with respect to the spatial extent of spontaneous and evoked quantal release within regions of amphibian motor-nerve terminal branches delineated by FM1-43 stained vesicle clusters (blobs). Discrete concentrations of vesicles revealed ∼2 μm apart along the length of terminal branches through FM1-43 staining were identical in size and spacing to those identified along terminal branches with SV2 antibody (AbSV2). Fluorescent antibodies to syntaxin 1 (AbS), SNAP-25 (AbS25) and the calcium channel α1B subunit (Abα1B) were found in relatively high concentrations coincident with the AbSV2 blobs. Three extracellular recording electrodes were placed in the vicinity of individual FM1-43 blobs, and an algorithm was used to determine the spatial origin of miniature endplate potentials (MEPPs) and EPPs together with their relative amplitudes. MEPPs and EPPs originated throughout the region stained by FM1-43 but not elsewhere; amplitude-frequency distributions of MEPPs and EPPs were similar for all FM1-43 blobs with average coefficients of variation of no less than 0.28. A linear relationship existed between the size of an FM1-43 blob, measured as the integrated extent of FM1-43 staining of a blob, and the frequency of MEPPs as well as the probability of EPPs from the blob. There was a proximo-distal gradient in the size of FM1-43 blobs along the length of single terminal branches, suggesting a gradient in release probability along the branches. The frequency distribution of the distances between blobs was approximately Gaussian, whereas the frequency distribution of the size of blobs was highly skewed and was best fitted with a gamma distribution. It is concluded that there are correlations among the extent of labeling of SNAP-25, syntaxin and calcium channels at a release site, the store of vesicles to be found there, and the probability of spontaneous and evoked quantal release.
Prediction and Compensation by an Internal Model for Back Forces During Finger Opening in an Overarm Throw
Authors: Hore J. , Watts S. , Tweed D.
Published: December 2017

Previous studies have indicated that timing of finger opening in an overarm throw is likely controlled centrally, possibly by means of an internal model of hand trajectory. The present objective was to extend the study of throwing to an examination of the dynamics of finger opening. Throwing a heavy ball and throwing a light ball presumably require different neural commands, because the weight of the ball affects the mechanics of the arm, and particularly, the mechanics of the finger. Yet finger control is critical to the accuracy of an overarm throw. We hypothesized that finger opening in an overarm throw is controlled by a central mechanism that uses an internal model to predict and compensate for movement-dependent back forces on the fingers. To test this idea we determined whether finger motion is affected by back forces, i.e., whether larger back forces cause larger finger extensions. Back forces were varied by having subjects throw, at the same fast speed, tennis-sized balls of different weights (14, 55, and 196 g). Arm- and finger-joint rotations were recorded with the search-coil technique; forces on the middle finger were measured with force transducers. Recordings showed that during ball release, the middle finger experienced larger back forces in throws with heavier balls. Nevertheless, most subjects showed proximal interphalangeal joint extensions that were unchanged or actually smaller with the heavier balls. This was the case for the first throw and for all subsequent throws with a ball of a new weight. This suggests that the finger flexors compensated for the larger back forces by exerting larger torques during finger extension. Supporting this view, at the moment of ball release, all finger joints flexed abruptly due to the now unopposed torques of the finger flexors, and the amplitude of this flexion was proportional to ball weight. We conclude that in overarm throws made with balls of different weights, the CNS predicts the different back forces from the balls and adjusts finger flexor torques accordingly. This is consistent with the view that finger opening in overarm throws is controlled by means of an internal model of the motor apparatus and the external load.
Effect of Extracellular pH on GABA-Activated Current in Rat Recombinant Receptors and Thin Hypothalamic Slices
Authors: Huang Ren-Qi , Dillon Glenn H.
Published: December 2017

We studied the effects of extracellular pH (pHo) on γ-aminobutyric acid (GABA)–mediated Cl− current in rat hypothalamic neurons and recombinant type-A GABA (GABAA) receptors stably expressed in human embryonic kidney cells (HEK 293), using whole cell and outside-out patch-clamp recordings. In α3β2γ2s receptors, acidic pH decreased, whereas alkaline pH increased the response to GABA in a reversible and concentration-dependent manner. Acidification shifted the GABA concentration-response curve to the right, significantly increasing the EC50 for GABA without appreciably changing the slope or maximal current induced by GABA. We obtained similar effects of pH in α1β2γ2 receptors and in GABA-activated currents recorded from thin hypothalamic brain slices. In outside-out patches recorded from α3β2γ2 recombinant receptors, membrane patches were exposed to 5 μM GABA at control (7.3), acidic (6.4), or alkaline (8.4) pH. GABA activated main and subconductance states of 24 and 16 pS, respectively, in α3β2γ2 receptors. Alkaline pHo increased channel opening frequency and decreased the duration of the long closed state, resulting in an increase in open probability (from 0.0801 ± 0.015 in pH 7.3 to 0.138 ± 0.02 in pH 8.4). Exposure of the channels to acidic pHo had the opposite effects on open probability (decreased to 0.006 ± 0.0001). Taken together, our results indicate that the function of GABAA receptors is modulated by extracellular pH. The proton effect is similar in recombinant and native receptors and is dependent on GABA concentration. In addition, the effect appears to be independent of the α-subunit isoform, and is due to the ability of H+ to alter the frequency of channel opening. Our findings indicate that GABAergic signaling in the CNS may be significantly altered during conditions that increase or decrease pH.
Human Eye-Head Gaze Shifts in a Distractor Task. II. Reduced Threshold for Initiation of Early Head Movements
Authors: Corneil Brian D. , Munoz Douglas P.
Published: December 2017

This study was motivated by the observation of early head movements(EHMs) occasionally generated before gaze shifts. Human subjects were presented with a visual or auditory target, along with an accompanying stimulus of the other modality, that either appeared at the same location as the target (enhancer condition) or at the diametrically opposite location (distractor condition). Gaze shifts generated to the target in the distractor condition sometimes were preceded by EHMs directed either to the side of the target ( correct EHMs) or the side of the distractor ( incorrect EHMs). During EHMs, the eyes performed compensatory eye movements to keep gaze stable. Incorrect EHMs were usually between 1 and 5° in amplitude and reached peak velocities generally <50°/s. These metrics increased for more eccentric distractors. The dynamics of incorrect EHMs initially followed a trajectory typical of much larger head movements. These results suggest that incorrect EHMs are head movements that initially were planned to orient to the peripheral distractor. Furthermore gaze shifts preceded by incorrect EHMs had longer reaction latencies than gaze shifts not preceded by incorrect EHMs, suggesting that the processes leading to incorrect EHMs also serve to delay gaze-shift initiation. These results demonstrate a form of distraction analogous to the incorrect gaze shifts (IGSs) described in the previous paper and suggest that a motor program encoding a gaze shift to a distractor is capable of initiating either an IGS or an incorrect EHM. A neural program not strong enough to initiate an IGS nevertheless can initiate an incorrect EHM.
Mauthner and Reticulospinal Responses to the Onset of Acoustic Pressure and Acceleration Stimuli
Authors: Casagrand Janet L. , Guzik Audrey L. , Eaton Robert C.
Published: December 2017

We determined how the Mauthner cell and other large, fast-conducting reticulospinal neurons of the goldfish responded to acoustic stimuli likely to be important in coordinating body movements underlying escape. The goal was to learn about the neurophysiological responses to these stimuli and the underlying processes of sensorimotor integration. We compared the intracellularly recorded postsynaptic responses (PSPs) of 9 Mauthner cells and a population of 12 other reticulospinal neurons to acoustic pressure and acceleration stimuli. All recorded cells received both pressure and acceleration inputs and responded to stimuli regardless of initial polarity. Thus these cells receive acoustic components necessary to determine source direction. We observed that the Mauthner cell was broadly tuned to acoustic pressure from 100 to 2,000 Hz, with a Q10dBof 0.5–1.1 over the best frequency range, 400–800 Hz. This broad tuning is probably due to input from S1 afferents and is similar to tuning of the behavioral audiogram. Our data suggest that cells have relatively more sustained responses to acceleration than to pressure stimuli, to which they rapidly adapted. For a given cell, PSP latencies and amplitudes varied inversely with stimulus intensity. For the entire population of cells studied, minimum onset latencies (i.e., those at the highest intensities) ranged from 0.7 to 7.6 ms for acoustic pressure and 0.7 to 9.8 ms for acceleration. This distribution in minimum onset latencies is consistent with earlier EMG and kinematic findings and supports our previous hypothesis that escape trajectory angle is controlled, in part, by varying the activation time of neurons in the escape network. While the Mauthner cell latency did not differ to both onset polarities of pressure and acceleration, this was not true of all cells. Also, the Mauthner cell responses to pressure were ∼0.6 ms faster than to acceleration; for the other cells, this difference was 1.1 ms with some cells having differences ≤3 ms. To both pressure and acceleration, the average, minimum Mauthner cell latency was ∼1 ms faster than the average of the 12 other cells. These data are consistent with the hypothesis that the Mauthner cell fires first, followed by other reticulospinal neurons, which more finely regulate escape trajectory. Finally, analysis of our results suggests that while pressure is more important in depolarizing the cell near threshold, high levels of acceleration, perhaps from fluid flow, may be very important in activating the system in a directional manner.
Features of Cortically Evoked Swallowing in the Awake Primate (Macaca fascicularis)
Authors: Martin Ruth E. , Kemppainen Pentti , Masuda Yuji , Yao Dongyuan , Murray Gregory M. , Sessle Barry J.
Published: December 2017

Although the cerebral cortex has been implicated in the control of swallowing, the output organization of the cortical swallowing representation, and features of cortically evoked swallowing, remain unclear. The present study defined the output features of the primate “cortical swallowing representation” with intracortical microstimulation (ICMS) applied within the lateral sensorimotor cortex. In four hemispheres of two awake monkeys, microelectrode penetrations were made at ≤1-mm intervals, initially within the face primary motor cortex (face-MI), and subsequently within the cortical regions immediately rostral, lateral, and caudal to MI. Two ICMS pulse trains [35-ms train, 0.2-ms pulses at 333 Hz, ≤30 μA (short train stimulus, T/S); 3- to 4-s train, 0.2-ms pulses at 50 Hz, ≤60 μA (continuous stimulus, C/S)] were applied at ≤500-μm intervals along each microelectrode penetration to a depth of 8–10 mm, and electromyographic (EMG) activity was recorded simultaneously from various orofacial and laryngeal muscles. Evoked orofacial movements, including swallowing, were verified by EMG analysis, and T/S and C/S movement thresholds were determined. Effects of varying ICMS intensity on swallow-related EMG properties were examined by applying suprathreshold C/S at selected intracortical sites. EMG patterns of swallows evoked from various cortical regions were compared with those of natural swallows recorded as the monkeys swallowed liquid and solid material. Results indicated that swallowing was evoked by C/S at ∼20% of 1,569 intracortical sites where ICMS elicited an orofacial motor response in both hemispheres of the two monkeys, typically at C/S intensities ≤30 μA. In contrast, swallowing was not evoked by T/S in either monkey. Swallowing was evoked from four cortical regions: the ICMS-defined face-MI, the face primary somatosensory cortex (face-SI), the region lateral and anterior to face-MI corresponding to the cortical masticatory area (CMA), and an area >5 mm deep to the cortical surface corresponding to both the white matter underlying the CMA and the frontal operculum; EMG patterns of swallows elicited from these four cortical regions showed some statistically significant differences. Whereas swallowing only was evoked at some sites, particularly within the deep cortical area, swallowing was more frequently evoked together with other orofacial responses including rhythmic jaw movements. Increasing ICMS intensity increased the magnitude, and decreased the latency, of the swallow-related EMG burst in the genioglossus muscle at some sites. These findings suggest that a number of distinct cortical foci may participate in the initiation and modulation of the swallowing synergy as well as in integrating the swallow within the masticatory sequence.
Angiotensin II Decreases Neuronal Delayed Rectifier Potassium Current: Role of Calcium/Calmodulin-Dependent Protein Kinase II
Authors: Zhu Mingyan , Gelband Craig H. , Posner Philip , Sumners Colin
Published: December 2017

Angiotensin II (Ang II) acts at specific receptors located on neurons in the hypothalamus and brain stem to elicit alterations in blood pressure, fluid intake, and hormone secretion. These actions of Ang II are mediated via Ang II type 1 (AT1) receptors and involve modulation of membrane ionic currents and neuronal activity. In previous studies we utilized neurons cultured from the hypothalamus and brain stem of newborn rats to investigate the AT1receptor–mediated effects of Ang II on neuronal K+currents. Our data indicate that Ang II decreases neuronal delayed rectifier (Kv) current, and that this effect is partially due to activation of protein kinase C (PKC), specifically PKCα. However, the data also indicated that another Ca2+-dependent mechanism was also involved in addition to PKC. Because Ca2+/calmodulin-dependent protein kinase II (CaM KII) is a known modulator of K+currents in neurons, we investigated the role of this enzyme in the AT1receptor–mediated reduction of neuronal Kv current by Ang II. The reduction of neuronal Kv current by Ang II was attenuated by selective inhibition of either calmodulin or CaM KII and was mimicked by intracellular application of activated (autothiophosphorylated) CaM KIIα. Concurrent inhibition of CaM KII and PKC completely abolished the reduction of neuronal Kv by Ang II. Consistent with these findings is the demonstration that Ang II increases CaM KII activity in neuronal cultures, as evidenced by increased levels of autophosphorylated CaM KIIα subunit. Last, single-cell reverse transcriptase (RT)-PCR analysis revealed the presence of AT1receptor-, CaM KIIα-, and PKCα subunit mRNAs in neurons that responded to Ang II with a decrease in Kv current. The present data indicate that the AT1receptor–mediated reduction of neuronal Kv current by Ang II involves a Ca2+/calmodulin/CaM KII pathway, in addition to the previously documented involvement of PKC.