bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance of Retinal Extracellular Space to Ca2+Level Decrease: Implications for the Synaptic Effects of Divalent Cations
Authors: Dmitriev Andrey , Pignatelli Angela , Piccolino Marco
Published: December 2017

Ion-sensitive microelectrodes were used to measure the variations of [Ca2+]o induced by application of low Ca2+ media in the superfused eyecup preparation of the Pseudemys turtle. The aim of the experiments was to evaluate the possibility, suggested by previous studies, that in the deep, sclerad, layers of the retina [Ca2+]omay remain high enough to sustain chemical synaptic transmission even after prolonged application of low-Ca2+ saline. It was found that, at depths of 100–200 μm from the vitreal surface, [Ca2+ ]o did not fall below 1 mM even after application for periods of 30–60 min of nominally Ca2+-free media, and it was >0.3 mM after 30-min application of media containing EGTA and with a Ca2+concentration of 1 nM. Previous studies in isolated salamander photoreceptors have shown that a reduction of [Ca2+]o to 0.3–1.0 mM may result in a paradoxical increase of Ca2+ influx into synaptic terminals due to the reduced screening of negative charge on the external face of the plasma membrane. On the basis of these results, the persistence or enhancement of synaptic transmission from photoreceptors to horizontal cells observed in various retinas treated with low-Ca2+ media may be accounted for within the classical Ca2+-dependent theory of synaptic transmission without invoking a Ca2+-independent mechanism.
Receptive Field Properties of Single Neurons in Rat Primary Visual Cortex
Authors: Girman Sergej V. , Sauvé Yves , Lund Raymond D.
Published: December 2017

The rat is used widely to study various aspects of vision including developmental events and numerous pathologies, but surprisingly little is known about the functional properties of single neurons in the rat primary visual cortex (V1). These were investigated in the anesthetized (Hypnorm-Hypnovel), paralyzed animal by presenting gratings of different orientations, spatial and temporal frequencies, dimensions, and contrasts. Stimulus presentation and data collection were automated. Most neurons (190/205) showed sharply tuned (≤30° bandwidth at half height) orientation selectivity with a bias for horizontal stimuli (31%). Analysis of response modulation of oriented cells showed a bimodal distribution consistent with the distinction between simple and complex cell types. Orientation specific interactions occurred between the center and the periphery of receptive fields, usually resulting in strong inhibition to center stimulation when both stimuli had the same orientation. There was no evidence for orientation columns nor for orderly change in optimal orientation with tangential tracks through V1. Responses were elicited by spatial frequencies ranging from zero (no grating) to 1.2 cycle/degree (c/°), peaking at 0.1 c/°, and with a modal cutoff of 0.6 c/°. Half of the neurons responded optimally to drifting gratings rather than flashing uniform field stimuli. Directional preference was seen for 59% of oriented units at all depths in the cortex. Optimal stimuli velocities varied from 10 to 250°/s. Some units, mainly confined to layer 4, responded to velocities as high as 700°/s. Response versus contrast curves (best fit with Naka-Rushton) varied from nearly linear to extremely steep (mean contrast semisaturation 50% and threshold 6%). There was a trend for cells from superficial layers to be more selective to different stimulus parameters than deeper layers cells. We conclude that neurons in rat V1 have complex and diverse visual properties, necessary for precise visual form perception with low spatial resolution.
Glycinergic Miniature Synaptic Currents and Receptor Cluster Sizes Differ Between Spinal Cord Interneurons
Authors: Oleskevich Sharon , Alvarez Francisco J. , Walmsley Bruce
Published: December 2017

The structural features of a synaptic connection between central neurons play an important role in determining the strength of the connection. In the present study, we have examined the relationship between the structural and functional properties of glycinergic synapses in the rat spinal cord. We have analyzed the structure of glycinergic receptor clusters on rat ventral horn interneurons using antibodies against the glycine receptor clustering protein, gephyrin. We have examined the properties of quantal glycinergic currents generated at these synapses using whole cell patch-clamp recordings of miniature postsynaptic inhibitory currents (mIPSCs) in rat spinal cord slices in vitro. Our immunolabeling results demonstrate that there is a considerable variability in the size of glycine receptor clusters within individual neurons. Furthermore there are large differences in the mean cluster size between neurons. These observations are paralleled closely by recordings of glycinergic mIPSCs. The mIPSC amplitude varies significantly within and between neurons. Results obtained using combined immunolabeling and electrophysiological recording on the same neurons show that cells with small glycine receptor clusters concurrently exhibit small mIPSCs. Our results suggest that the differences in the size of glycinergic receptor clusters may constitute an important factor contributing to the observed differences in mIPSC amplitude among spinal cord interneurons.
Responses to Auditory Stimuli in Macaque Lateral Intraparietal Area II. Behavioral Modulation
Authors: Linden Jennifer F. , Grunewald Alexander , Andersen Richard A.
Published: December 2017

The lateral intraparietal area (LIP), a region of posterior parietal cortex, was once thought to be unresponsive to auditory stimulation. However, recent reports have indicated that neurons in area LIP respond to auditory stimuli during an auditory-saccade task. To what extent are auditory responses in area LIP dependent on the performance of an auditory-saccade task? To address this question, recordings were made from 160 LIP neurons in two monkeys while the animals performed auditory and visual memory-saccade and fixation tasks. Responses to auditory stimuli were significantly stronger during the memory-saccade task than during the fixation task, whereas responses to visual stimuli were not. Moreover, neurons responsive to auditory stimuli tended also to be visually responsive and to exhibit delay or saccade activity in the memory-saccade task. These results indicate that, in general, auditory responses in area LIP are modulated by behavioral context, are associated with visual responses, and are predictive of delay or saccade activity. Responses to auditory stimuli in area LIP may therefore be best interpreted as supramodal responses, and similar in nature to the delay activity, rather than as modality-specific sensory responses. The apparent link between auditory activity and oculomotor behavior suggests that the behavioral modulation of responses to auditory stimuli in area LIP reflects the selection of auditory stimuli as targets for eye movements.
Adaptive Changes in Motor Activity Associated With Functional Recovery Following Muscle Denervation in Walking Cats
Authors: Pearson K. G. , Fouad K. , Misiaszek J. E.
Published: December 2017

In this investigation we examined the changes in the pattern of activity in the medial gastrocnemius (MG) muscle in walking cats following transection of the nerves innervating synergist muscles (lateral gastrocnemius, soleus, and plantaris). Immediately following the nerve transections, there was a large increase in ankle flexion during early stance (from ∼10 to ∼30°) and a marked increase in the magnitude of the MG bursts during stance. We attribute this increase in the magnitude of the MG bursts to an increase in afferent feedback from the abnormally stretched MG muscle. During the week after the nerve transections, there was a progressive decrease in ankle yield. This improvement in ankle function was correlated with an increase in magnitude of two components of the MG bursts; the initial component starting during late swing and ending ∼40 ms after ground contact, and a late component associated with stance. The time courses of the increases in the initial and late components of the MG bursts were different. Large and significant increases in the late component occurred the day after the nerve transections, whereas increases in the initial component occurred more gradually. This difference in time course was reflected in the kinematics of ankle movement. Over the first few days after the nerve transections, improvement in ankle movement occurred primarily late in the stance phase, and there was little change in ankle yield during early stance. At 1 wk, however, there was a significant reduction in ankle yield during early stance. This decreased yield was most likely due to an increase in stiffness of the MG muscle at the time of ground contact resulting from the increase in magnitude of the initial component of the MG bursts. The increases in the magnitude of the initial and late components of the MG bursts, as well as the improvement in ankle function, depended on use of the leg. All these changes were delayed by immobilizing the leg for 6 days in an extended position. We discuss possible mechanisms underlying the increase in the magnitude of the MG bursts and propose that proprioceptive signals from the stretched MG muscles provide an error signal for rescaling the magnitude of the centrally generated initial component. Our data support the concept that proprioceptive feedback functions to scale the magnitude of feed-forward motor commands to ensure they are appropriate for the biomechanical properties of the musculoskeletal system.
Activity-Dependent Depression of GABAergic IPSCs in Cultured Hippocampal Neurons
Authors: Jensen Kimmo , Lambert John D. C. , Jensen Morten Skovgaard
Published: December 2017

Short-term depression of monosynaptic GABAergic inhibitory postsynaptic currents (IPSCs) evoked between pairs of cultured rat hippocampal neurons was investigated using dual whole cell patch-clamp recordings. Paired stimuli applied to the GABAergic neuron resulted in paired-pulse depression (PPD) of the second IPSC (IPSC2) at interpulse intervals from 25 to 2,000 ms. CGP 55845A, but not CGP 35348, reduced PPD marginally. Brief paired-pulse applications of exogenous GABA indicated that postsynaptic factors made only minimal contribution to PPD of IPSCs. IPSC1 and PPD was reduced on lowering [Ca2+]o and enhanced on increasing [Ca2+]o. The potassium-channel blocker 4-aminopyridine (4-AP), which increases presynaptic Ca2+ influx, enhanced IPSC1 and PPD. Chelation of residual Ca2+ in the GABAergic boutons with EGTA-AM enhanced PPD. Stimulation of the presynaptic neuron at frequencies ( f) ranging from 2.5 to 80 Hz resulted in tetanic depression of IPSCs, which declined rapidly and reached a plateau depending on f and [Ca2+]o. CGP 55845A decreased tetanic depression in the first part of the train, but this could be overcome with continued stimulation. We show that GABAergic IPSCs are robustly depressed by paired-pulse stimulation in cultured hippocampal neurons. The depression of IPSCs is mainly independent of presynaptic GABAB receptors and could be caused by depletion of releasable vesicles. Depleted synapses recover with a slow time course, depending on factors that regulate [Ca2+]i in the GABAergic boutons.
Spontaneous Action Potentials Initiate Rhythmic Intercellular Calcium Waves in Immortalized Hypothalamic (GT1–1) Neurons
Authors: Costantin James L. , Charles Andrew C.
Published: December 2017

GT1–1 cells exhibit spontaneous action potentials and transient increases in intracellular calcium concentration ([Ca2+]i) that occur in individual cells and as spatially propagated intercellular Ca2+ waves. In this study, simultaneous cell-attached patch-clamp recording of action currents (indicative of action potentials) and fluorescence imaging of [Ca2+]i revealed that Ca2+transients in GT1–1 cells were preceded by a single action current or a burst of action currents. Action currents preceded Ca2+transients in a similar pattern regardless of whether the Ca2+ transients were limited to the individual cell or occurred as part of an intercellular Ca2+ wave. Both the action currents and Ca2+ transients were abolished by 1 μM tetrodotoxin. Removal of extracellular Ca2+ abolished all spontaneous Ca2+ transients without inhibiting the firing of action currents. Nimodipine, which blocks L-type Ca2+ currents in GT1–1 cells, also abolished all spontaneous Ca2+ signaling. Delivery of small voltage steps to the patch pipette in the cell-attached configuration elicited action currents the latency to firing of which decreased with increasing amplitude of the voltage step. These results indicate that spontaneous intercellular Ca2+ waves are generated by a propagated depolarization, the firing of action potentials in individual cells, and the resulting influx of Ca2+ through L-type Ca2+ channels. These patterns of spontaneous activity may be important in driving the pulsatile release of GnRH from networks of cells.
Antibodies Against Cysteine String Proteins Inhibit Evoked Neurotransmitter Release at Xenopus Neuromuscular Junctions
Authors: Poage Robert E. , Meriney Stephen D. , Gundersen Cameron B. , Umbach Joy A.
Published: December 2017

Cysteine string proteins (CSPs) are evolutionarily conserved proteins that are associated with synaptic vesicles and other regulated secretory organelles. To investigate the role of CSPs in vertebrate neuromuscular transmission, we introduced anti-CSP antibodies into the cell bodies of Xenopus spinal motor neurons that form synapses with embryonic muscle cells in culture. These antibodies produced a rapid (within 3–6 min), and in most cases complete, inhibition of stimulus-dependent neurotransmitter secretion. However, spontaneous neurotransmitter release was stable (both in frequency and amplitude) throughout the period of antibody exposure. Several control experiments validated the specificity of the anti-CSP antibody effects. First, the anti-CSP antibody actions were not mimicked either by antibodies against another synaptic vesicle protein SV2, or by nonspecific immunoglobins. Second, heat treatment of the anti-CSP antibodies eliminated their effect on evoked secretion. Third, immunoblot experiments showed that the anti-CSP and anti-SV2 antibodies were highly selective for their respective antigens in these Xenopus cultures. We conclude from these results that CSPs are vital constituents of the pathway for regulated neurotransmitter release in vertebrates. Moreover, the selective inhibition of evoked, but not spontaneous transmitter release by anti-CSP antibodies indicates that there is a fundamental difference in the machinery that mediates these secretory processes.
Multimodal Convergence of Presynaptic Afferent Inhibition in Insect Proprioceptors
Authors: Stein Wolfgang , Schmitz Josef
Published: December 2017

In the leg motor system of insects, several proprioceptive sense organs provide the CNS with information about posture and movement. Within one sensory organ, presynaptic inhibition shapes the inflow of sensory information to the CNS. We show here that also different proprioceptive sense organs can exert a presynaptic inhibition on each other. The afferents of one leg proprioceptor in the stick insect, either the position-sensitive femoral chordotonal organ or the load-sensitive campaniform sensilla, receive a primary afferent depolarization (PAD) from two other leg proprioceptors, the campaniform sensilla and/or the coxal hairplate. The reversal potential of this PAD is about −59 mV, and the PAD is associated with a conductance increase. The properties of this presynaptic input support the hypothesis that this PAD acts as presynaptic inhibition. The PAD reduces the amplitude of afferent action potentials and thus likely also afferent transmitter release and synaptic efficacy. These findings imply that PAD mechanisms of arthropod proprioceptors might be as complex as in vertebrates.
Serotonergic Modulation of Neurotransmission in the Rat Basolateral Amygdala
Authors: Rainnie Donald G.
Published: December 2017

Whole cell patch-clamp recordings were obtained from projection neurons and interneurons of the rat basolateral amygdala (BLA) to understand local network interactions in morphologically identified neurons and their modulation by serotonin. Projection neurons and interneurons were characterized morphologically and electrophysiologically according to their intrinsic membrane properties and synaptic characteristics. Synaptic activity in projection neurons was dominated by spontaneous inhibitory postsynaptic currents (IPSCs) that were multiphasic, reached 181 ± 38 pA in amplitude, lasted 296 ± 27 mS, and were blocked by the GABAA receptor antagonist, bicuculline methiodide (30 μM). In interneurons, spontaneous synaptic activity was characterized by a burst-firing discharge patterns (200 ± 40 Hz) that correlated with the occurrence of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive, high-amplitude (260 ± 42 pA), long-duration (139 ± 19 mS) inward excitatory postsynaptic currents (EPSCs). The interevent interval of 831 ± 344 mS for compound inhibitory postsynaptic potentials (IPSPs), and 916 ± 270 mS for EPSC bursts, suggested that spontaneous IPSP/Cs in projection neurons are driven by burst of action potentials in interneurons. Hence, BLA interneurons may regulate the excitability of projection neurons and thus determine the degree of synchrony within ensembles of BLA neurons. In interneurons 5-hydroxytryptamine oxalate (5-HT) evoked a direct, dose-dependent, membrane depolarization mediated by a 45 ± 6.9 pA inward current, which had a reversal potential of −90 mV. The effect of 5-HT was mimicked by the 5-HT2 receptor agonist, α-methyl-5-hydroxytryptamine (α-methyl-5-HT), but not by the 5-HT1A receptor agonist, (±) 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), or the 5-HT1B agonist, CGS 12066A. In projection neurons, 5-HT evoked an indirect membrane hyperpolarization (∼2 mV) that was associated with a 75 ± 42 pA outward current and had a reversal potential of −70 mV. The response was independent of 5-HT concentration, blocked by TTX, mimicked by α-methyl-5-HT but not by 8-OH-DPAT. In interneurons, 5-HT reduced the amplitude of the evoked EPSC and in the presence of TTX (0.6 μM) reduced the frequency of miniature EPSCs but not their quantal content. In projection neurons, 5-HT also caused a dose-dependent reduction in the amplitude of stimulus evoked EPSCs and IPSCs. These results suggest that acute serotonin release would directly activate GABAergic interneurons of the BLA, via an activation of 5-HT2 receptors, and increase the frequency of inhibitory synaptic events in projection neurons. Chronic serotonin release, or high levels of serotonin, would reduce the excitatory drive onto interneurons and may act as a feedback mechanism to prevent excess inhibition within the nucleus.
Vertical Cell Responses to Sound in Cat Dorsal Cochlear Nucleus
Authors: Rhode William S.
Published: December 2017

The dorsal cochlear nucleus receives input from the auditory nerve and relays acoustic information to the inferior colliculus. Its principal cells receive two systems of inputs. One system through the molecular layer carries multimodal information that is processed through a neuronal circuit that resembles the cerebellum. A second system through the deep layer carries primary auditory nerve input, some of which is relayed through interneurons. The present study reveals the morphology of individual interneurons and their local axonal arbors and how these inhibitory interneurons respond to sound. Vertical cells lie beneath the fusiform cell layer. Their dendritic and axonal arbors are limited to an isofrequency lamina. They give rise to pericellular nests around the base of fusiform cells and their proximal basal dendrites. These cells exhibit an onset-graded response to short tones and have response features defined as type II. They have tuning curves that are closed contours (0 shaped), thresholds ∼27 dB SPL, spontaneous firing rates of ∼0 spikes/s, and they respond weakly or not at all to broadband noise, as described for type II units. Their responses are nonmonotonic functions of intensity with peak responses between 30 and 60 dB SPL. They also show a preference for the high-to-low direction of a frequency sweep. It has been suggested that these circuits may be involved in the processing of spectral cues for the localization of sound sources.
Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons
Authors: Liu Qing-Song , Patrylo Peter R. , Gao Xiao-Bing , van den Pol Anthony N.
Published: December 2017

Recent reports suggest that kainate acting at presynaptic receptors reduces the release of the inhibitory transmitter GABA from hippocampal neurons. In contrast, in the hypothalamus in the presence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor antagonists [1-(4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) and d,l-2-amino-5-phosphonopentanoic acid (AP5)], kainate increased GABA release. In the presence of tetrodotoxin, the frequency, but not the amplitude, of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) was enhanced by kainate, consistent with a presynaptic site of action. Postsynaptic activation of kainate receptors on cell bodies/dendrites was also found. In contrast to the hippocampus where kainate increases excitability by reducing GABA release, in the hypothalamus where a much higher number of GABAergic cells exist, kainate-mediated activation of transmitter release from inhibitory neurons may reduce the level of neuronal activity in the postsynaptic cell.
Fictive Rhythmic Motor Patterns Induced by NMDA in an In Vitro Brain Stem–Spinal Cord Preparation From an Adult Urodele
Authors: Delvolvé Isabelle , Branchereau Pascal , Dubuc Réjean , Cabelguen Jean-Marie
Published: December 2017

An in vitro brain stem–spinal cord preparation from an adult urodele ( Pleurodeles waltl) was developed in which two fictive rhythmic motor patterns were evoked by bath application of N-methyl-d-aspartate (NMDA; 2.5–10 μM) with d-serine (10 μM). Both motor patterns displayed left-right alternation. The first pattern was characterized by cycle periods ranging between 2.4 and 9.0 s (4.9 ± 1.2 s, mean ± SD) and a rostrocaudal propagation of the activity in consecutive ventral roots. The second pattern displayed longer cycle periods (8.1–28.3 s; 14.2 ± 3.6 s) with a caudorostral propagation. The two patterns were inducible after a spinal transection at the first segment. Preliminary experiments on small pieces of spinal cord further suggested that the ability for rhythm generation is distributed along the spinal cord of this preparation. This study shows that the in vitro brain stem–spinal cord preparation from Pleurodeles waltl may be a useful model to study the mechanisms underlying the different axial motor patterns and the flexibility of the neural networks involved.
Group I mGluR-Mediated Silent Induction of Long-Lasting Epileptiform Discharges
Authors: Merlin Lisa R.
Published: December 2017

Picrotoxin, an antagonist of GABAAreceptor-mediated activity, elicited 320- to 475-ms synchronized bursts from the CA3 region of the guinea pig hippocampal slice. The addition of the selective group I metabotropic glutamate receptor (mGluR) agonist ( S)-3,5-dihydroxyphenylglycine (DHPG, 50 μM; 20- to 45-min application) gradually increased the burst duration to 1–4 s; this effect persisted 2–3 h after agonist removal. To determine whether the induction of this long-lasting effect required ongoing synchronized activity during mGluR activation, DHPG application in a second set of experiments took place in the presence of CNQX and ( R,S)-CPP, antagonists of AMPA/kainate and NMDA receptors, respectively. In these experiments, synchronized bursting was silenced during the mGluR agonist application, yet after wash out of the DHPG and the ionotropic glutamate receptor (iGluR) blockers, epileptiform discharges 1–10 s in duration appeared and persisted at least 2 h after wash out of the mGluR agonist. The potentiated bursts were reversibly shortened by application of 500–1,000 μM (+)-α-methyl-4-carboxyphenylglycine (MCPG) or ( S)-4-carboxyphenylglycine (4CPG), agents with group I mGluR antagonist activity. These data suggest that transient activation of group I mGluRs, even during silencing of synchronized epileptiform activity, may have an epileptogenic effect, converting brief interictal-length discharges into persistent seizure-length events. The induction process is iGluR independent, and the maintenance is largely mediated by the action of endogenous glutamate on group I mGluRs, suggesting that autopotentiation of the group I mGluR-mediated response may underlie the epileptogenesis seen here.
Dopamine Depresses Synaptic Inputs Into the Olfactory Bulb
Authors: Hsia Albert Y. , Vincent Jean-Didier , Lledo Pierre-Marie
Published: December 2017

Both observations in humans with disorders of dopaminergic transmission and molecular studies point to an important role for dopamine in olfaction. In this study we found that dopamine receptor activation in the olfactory bulb causes a significant depression of synaptic transmission at the first relay between olfactory receptor neurons and mitral cells. This depression was found to be caused by activation of the D2 subtype of dopamine receptor and was reversible by a specific D2 receptor antagonist. A change in paired-pulse modulation during the depression suggests a presynaptic locus of action. The depression was found to occur independent of synaptic activity. These results provide the first evidence for dopaminergic control of inputs to the main olfactory bulb. The magnitude and locus of dopamine’s modulatory capabilities in the bulb suggest important roles for dopamine in odorant processing.
Locomotor Strategy for Pedaling: Muscle Groups and Biomechanical Functions
Authors: Raasch Christine C. , Zajac Felix E.
Published: December 2017

A group of coexcited muscles alternating with another group is a common element of motor control, including locomotor pattern generation. This study used computer simulation to investigate human pedaling with each muscle assigned at times to a group. Simulations were generated by applying patterns of muscle excitations to a musculoskeletal model that includes the dynamic properties of the muscles, the limb segments, and the crank load. Raasch et al. showed that electromyograms, pedal reaction forces, and limb and crank kinematics recorded during maximum-speed start-up pedaling could be replicated with two signals controlling the excitation of four muscle groups (1 group alternating with another to form a pair). Here a four-muscle-group control also is shown to replicate steady pedaling. However, simulations show that three signals controlling six muscle groups (i.e., 3 pairs) is much more biomechanically robust, such that a wide variety of forward and backward pedaling tasks can be executed well. We found the biomechanical functions necessary for pedaling, and how these functions can be executed by the muscle groups. Specifically, the phasing of two pairs with respect to limb extension and flexion and the transitions between extension and flexion do not change with pedaling direction. One pair of groups (uniarticular hip and knee extensors alternating with their anatomic antagonists) generates the energy required for limb and crank propulsion during limb extension and flexion, respectively. In the second pair, the ankle plantarflexors transfer the energy from the limb inertia to the crank during the latter part of limb extension and the subsequent limb extension-to-flexion transition. The dorsiflexors alternate with the plantarflexors. The phasing of the third pair (the biarticular thigh muscles) reverses with pedaling direction. In forward pedaling, the hamstring is excited during the extension-to-flexion transition and in backward pedaling during the opposite transition. In both cases hamstrings propel the crank posteriorly through the transition. Rectus femoris alternates with hamstrings and propels the crank anteriorly through the transitions. With three control signals, one for each pair of groups, different cadences (or power outputs) can be achieved by adjusting the overall excitatory drive to the pattern generating elements, and different pedaling goals (e.g., smooth, or energy-efficient pedaling; 1- or 2-legged pedaling) by adjusting the relative excitation levels among the muscle groups. These six muscle groups are suggested to be elements of a general strategy for pedaling control, which may be generally applicable to other human locomotor tasks.
Ca2+-Induced Ca2+Release Activates Spontaneous Miniature Outward Currents (SMOCs) in Parasympathetic Cardiac Neurons
Authors: Merriam Laura A. , Scornik Fabiana S. , Parsons Rodney L.
Published: December 2017

Mudpuppy parasympathetic cardiac neurons exhibit spontaneous miniature outward currents (SMOCs) that are thought to be due to the activation of clusters of large conductance Ca2+-activated K+channels (BK channels) by localized release of Ca2+from internal stores close to the plasma membrane. Perforated-patch whole cell recordings were used to determine whether Ca2+-induced Ca2+release (CICR) is involved in SMOC generation. We confirmed that BK channels are involved by showing that SMOCs are inhibited by 100 nM iberiotoxin or 500 μM tetraethylammonium (TEA), but not by 100 nM apamin. SMOC frequency is decreased in solutions that contain 0 Ca2+/3.6 mM Mg2+, and also in the presence of 1 μM nifedipine and 3 μM ω-conotoxin GVIA, suggesting that SMOC activation is dependent on calcium influx. However, Ca2+influx alone is not sufficient; SMOC activation is also dependent on Ca2+release from the caffeine- and ryanodine-sensitive Ca2+store, because exposure to 2 mM caffeine consistently caused an increase in SMOC frequency, and 10–100 μM ryanodine altered the configuration of SMOCs and eventually inhibited SMOC activity. Depletion of intracellular Ca2+stores by the Ca-ATPase inhibitor cyclopiazonic acid (10 μM) inhibited SMOC activity, even when Ca2+influx was not compromised. We also tested the effects of the membrane-permeable Ca2+chelators, bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid-AM (BAPTA-AM) and EGTA-AM. EGTA-AM (10 μM) caused no inhibition of SMOC activation, whereas 10 μM BAPTA-AM consistently inhibited SMOCs. After SMOCs were completely inhibited by BAPTA, 3 mM caffeine caused SMOC activity to resume. This effect was reversible on removal of caffeine and suggests that the source of Ca2+that triggers the internal Ca2+release channel is different from the source of Ca2+that activates clusters of BK channels. We propose that influx of Ca2+through voltage-dependent Ca2+channels is required for SMOC generation, but that the influx of Ca2+triggers CICR from intracellular stores, which then activates the BK channels responsible for SMOC generation.
Facial Taste Responses of the Channel Catfish to Binary Mixtures of Amino Acids
Authors: Ogawa K. , Caprio J.
Published: December 2017

We investigated the neural processing of binary gustatory mixtures of amino acids by the facial taste system of the channel catfish, Ictalurus punctatus. In vivo electrophysiological recordings indicated that the magnitude of both integrated and single-unit facial taste responses to binary mixtures of amino acids was greatest if the components bound to independent receptor sites. Facial taste responses were obtained from 32 multiunit and 55 single taste fiber preparations to binary mixtures of amino acids whose components bind to independent taste receptor sites (group I) or to the same or highly cross-reactive taste receptor sites (group II). All component stimuli were adjusted in concentration to provide approximately equal response magnitude as determined by either the height of the integrated multiunit taste response or by the number of action potentials generated/3 s of response time/single taste fiber. The mixture discrimination index (MDI), defined as the response to the mixture divided by the average of the responses to the component stimuli, was calculated for each test of a binary mixture. MDIs of group I binary mixtures for both the integrated multiunit and single fiber data were significantly greater than those for either the control or group II binary mixtures. In a subset of multiunit recordings, the MDIs of a group I binary mixture across three log units of stimulus concentration were similar and significantly greater than those of a group II binary mixture. Analysis of the single fiber data also indicated that the MDIs of group I binary mixtures were significantly larger than those of group II binary mixtures for both alanine-best and arginine-best taste fibers; however, the MDIs of group I binary mixtures calculated from recordings from arginine-best taste fibers were significantly greater than those recorded from alanine-best taste fibers.
Spectral Integration by Type II Interneurons in Dorsal Cochlear Nucleus
Authors: Spirou George A. , Davis Kevin A. , Nelken Israel , Young Eric D.
Published: December 2017

The type II unit is a prominent inhibitory interneuron in the dorsal cochlear nucleus (DCN), most likely recorded from vertical cells. Type II units are characterized by low rates of spontaneous activity, weak responses to broadband noise, and vigorous, narrowly tuned responses to tones. The weak responses of type II units to broadband stimuli are unusual for neurons in the lower auditory system and suggest that these units receive strong inhibitory inputs, most likely from onset-C neurons of the ventral cochlear nucleus. The question of the definition of type II units is considered here; the characteristics listed in the preceding text define a homogeneous type II group, but the boundary between this group and other low spontaneous rate neurons in DCN (type I/III units) is not yet clear. Type II units in decerebrate cats were studied using a two-tone paradigm to map inhibitory responses to tones and using noisebands of varying width to study the inhibitory processes evoked by broadband stimuli. Iontophoresis of bicuculline and strychnine and comparisons of two-tone responses between type II units and auditory nerve fibers were used to differentiate inhibitory processes occurring near the cell from two-tone suppression in the cochlea. For type II units, a significant inhibitory region is always seen with two-tone stimuli; the bandwidth of this region corresponds roughly to the previously reported excitatory bandwidth of onset-C neurons. Bandwidth widening experiments with noisebands show a monotonic decline in response as the bandwidth increases; these data are interpreted as revealing strong inhibitory inputs with properties more like onset-C neurons than any other response type in the lower auditory system. Consistent with these properties, iontophoresis of inhibitory antagonists produces a large increase in discharge rate to broadband noise, making tone and noise responses nearly equal.
Load-Independent Contributions From Motor-Unit Synchronization to Human Physiological Tremor
Authors: Halliday David M. , Conway Bernard A. , Farmer Simon F. , Rosenberg Jay R.
Published: December 2017

This study describes two load-independent rhythmic contributions from motor-unit synchronization to normal physiological tremor, which occur in the frequency ranges 1–12 Hz and 15–30 Hz. In common with previous studies, we use increased inertial loading to identify load-independent components of physiological tremor. The data consist of simultaneous recordings of tremor acceleration from the third finger, a surface electromyogram (EMG), and the discharges of pairs of single motor units from the extensor digitorum communis (EDC) muscle, collected from 13 subjects, and divided into 2 data sets: 106 records with the finger unloaded and 84 records with added mass from 5 to 40 g. Frequency domain analysis of motor-unit data from individual subjects reveals the presence of two distinct frequency bands in motor-unit synchronization, 1–12 Hz and 15–30 Hz. A novel Fourier-based population analysis demonstrates that the same two rhythmic components are present in motor-unit synchronization across both data sets. These frequency components are not related to motor-unit firing rates. The same frequency bands are present in the correlation between motor-unit activity and tremor and between surface EMG activity and tremor, despite a significant alteration in the characteristics of the tremor with increased inertial loading. A multivariate analysis demonstrates conclusively that motor-unit synchronization is the source of these contributions to normal physiological tremor. The population analysis suggests that single motor-unit discharges can predict an average of 10% of the total tremor signal in these two frequency bands. Rectified surface EMG can predict an average of 20% of the tremor; therefore within our population of recordings, the two components of motor-unit synchronization account for an average of 20% of the total tremor signal, in the frequency ranges 1–12 Hz and 15–30 Hz. Our results demonstrate that normal physiological tremor is a complex signal containing information relating to motor-unit synchronization in different frequency bands, and lead to a revised definition of normal physiological tremor during low force postural contractions, which is based on using both the tremor spectra and the correlation between motor-unit activity and tremor to characterize the load-dependent and the load-independent components of tremor. In addition, both physiological tremor and rectified EMG emerge as powerful predictors of the frequency components of motor-unit synchronization.
Reduction in Potassium Currents in Identified Cutaneous Afferent Dorsal Root Ganglion Neurons After Axotomy
Authors: Everill Brian , Kocsis Jeffery D.
Published: December 2017

Potassium currents have an important role in modulating neuronal excitability. We have investigated the effects of axotomy on three voltage-activated K+ currents, one sustained and two transient, in cutaneous afferent dorsal root ganglion (DRG) neurons. Fourteen to 21 days after axotomy, L4 and L5 DRG neurons were acutely dissociated and were studied 2–8 h after plating. Whole cell patch-clamp recordings were obtained from identified cutaneous afferent neurons (46–50 μm diam); K+ currents were isolated by blocking Na+ and Ca2+ currents with appropriate ion replacement and channel blockers. Separation of the current components was achieved on the basis of sensitivity to dendrotoxin or 4-aminopyridine and by the response to variation in conditioning voltage. Both control and injured neurons displayed qualitatively similar complex K+ currents composed of distinct kinetic and pharmacological components. Three distinct K+ current components, a sustained ( I K) and two transient ( I A and I D), were identified in variable proportions. However, total peak current was reduced by 52% in the axotomized cells when compared with control cells. Two current components were reduced after ligation, I Aby 60%, I K by over 65%, compared with control cells. I D appeared unaffected after acute ligation. These results indicate a large reduction in overall K+ current, resulting from reductions in I K and I A, on large cutaneous afferent neurons after nerve ligation and have implications for excitability changes of injured primary afferent neurons.
Ca2+-Activated Nonselective Cationic Current (I CAN) in Turtle Motoneurons
Authors: Perrier Jean-François , Hounsgaard Jørn
Published: December 2017

The presence of a calcium-activated nonspecific cationic (CAN) current in turtle motoneurons and its involvement in plateau potentials, bistability, and windup was investigated by intracellular recordings in a spinal cord slice preparation. In the presence of tetraethylammonium (TEA) and tetrodotoxin (TTX), calcium action potentials evoked by depolarizing current pulses were always followed by an afterdepolarization associated with a decrease in input resistance. The presence of the afterdepolarization depended on the calcium spike and not on membrane potential. Replacement of extracellular sodium by choline or N-methyl-d-glucamine (NMDG) reduced the afterdepolarization, confirming that it was mediated by a CAN current. Plateau potentials and windup were evoked in response to intracellular current pulses in the presence of agonist for different metabotropic receptors. Replacement of extracellular sodium by choline or NMDG did not abolish the generation of plateau potentials, bistability, or windup, showing that Na+ was not the principal charge carrier. It is concluded that plateau potentials, bistability and windup in turtle motoneurons do not depend on a CAN current even though its presence can be detected.
Cl− Accumulation Does Not Account for the Depolarizing Phase of the Synaptic GABA Response in Hippocampal Pyramidal Cells
Authors: Perkins Katherine L.
Published: December 2017

It has been proposed that the depolarizing phase of the biphasic synaptic GABA response could be mediated by HCO3 − passing through GABAA channels after dissipation of the transmembrane Cl− gradient due to intracellular Cl− accumulation. To test this hypothesis, giant GABA-mediated postsynaptic currents (GPSCs) were recorded from pyramidal cells in slices of adult guinea pig hippocampus in the presence of 4-aminopyridine. GPSCs consisted of an early outward current (GABAA component) followed by a late inward current (GABAD component). Spontaneous outward inhibitory postsynaptic currents (IPSCs) occurred during the GABADcomponent of the GPSC. GPSCs that were evoked 1–12 s after the preceding GPSC (short interval, siGPSCs) showed no GABADcomponent even though in many cells the amplitude of the siGPSC was greater than the amplitude of the GABAA component of the preceding spontaneous GPSC. In addition, the siGPSC evoked during the GABAD component of a spontaneous GPSC was an outward current. To test whether the siGPSC lacked a GABADcomponent because it was generated predominantly at the soma, where less of an increase in [Cl−]i would occur, picrotoxin was applied to the soma of the pyramidal cell. To the contrary, this focal application of picrotoxin caused less of a reduction in the amplitude of the siGPSC than in the amplitude of the GABAA component of the GPSC. Furthermore when a GPSC and siGPSC were evoked 10 s apart using identical stimuli, the area under the outward current curve was sometimes greater for the siGPSC than for the GPSC, and yet the siGPSC had no inward component. This result indicates that even when the location of Cl− entry was the same, more Cl− could enter the cell during the siGPSC than during the outward component of the GPSC and yet not lead to an inward current. In addition, when the second of two identical stimuli was applied during the inward GABAD component of the first evoked GPSC, the GABAA response it generated was always outward, demonstrating that the equilibrium potential for GABAA responses did not become more positive than the holding potential during a GPSC. Finally, evoking GPSCs at a hyperpolarized potential revealed that the siGPSC actually lacked a GABAD conductance. These results disprove the Cl− accumulation hypothesis of the synaptic depolarizing GABA response and suggest the possibility that a separate channel type may mediate the GABAD component of the GPSC.
Properties of Cholinergic Responses in Isolated Parapodial Muscle Fibers ofAplysia
Authors: Laurienti P. J. , Blankenship J. E.
Published: December 2017

The parapodial neuromuscular junction in the marine snail Aplysia brasiliana is a model synapse for the investigation of neural modulation. The parapodial muscle fibers are innervated by cholinergic motoneurons and by serotonergic modulatory cells. The physiological properties of voltage-gated currents of the muscle membranes and the effects of serotonin on these currents have been published previously. However, the pharmacological properties of the cholinergic receptors have not been investigated. Acetylcholine (ACh) applied exogenously to dissociated muscle fibers produces a response with a reversal potential of about −52 mV; the resting membrane potential of the average muscle fiber is approximately −56 mV. ACh induces variable responses (depolarizations or hyperpolarizations) in individual cells, but the transmitter never causes a depolarization adequate to produce muscle contraction. We demonstrate that the ACh response is the result of the activation of two distinct receptors. One receptor is linked to a chloride channel and induces a hyperpolarization with a reversal potential near −70 mV. This receptor is activated selectively by suberyldicholine and by nicotine and is antagonized by curare but not by hexamethonium. The second response, presumably caused by increased conductance to mixed cations, results in muscle fiber depolarization with a reversal potential near −35 mV and does induce muscle contraction. This receptor is activated by methylcarbamylcholine and selectively blocked by hexamethonium; atypically, this receptor is not activated by nicotine nor by carbachol. The depolarizing, cation-selective receptors likely are associated with identified excitatory cholinergic motoneurons the activity of which typically results in muscle contractions because the reversal potential for this ACh response is more depolarized than the activation threshold for voltage-gated calcium channels in these fibers. The hyperpolarizing, chloride-selective receptors may be associated with inhibitory motoneurons; such motoneurons have yet to be identified, but their presence is inferred because of the occurrence of spontaneous inhibitory junctional potentials recording from muscle fibers in situ. Muscle fiber responses to exogenously applied ACh reflect the relative contribution of each receptor type in each muscle fiber.
Electrophysiological Properties of Inferior Olive Neurons: A Compartmental Model
Authors: Schweighofer Nicolas , Doya Kenji , Kawato Mitsuo
Published: December 2017

As a step in exploring the functions of the inferior olive, we constructed a biophysical model of the olivary neurons to examine their unique electrophysiological properties. The model consists of two compartments to represent the known distribution of ionic currents across the cell membrane, as well as the dendritic location of the gap junctions and synaptic inputs. The somatic compartment includes a low-threshold calcium current ( I Ca_l), an anomalous inward rectifier current ( I h), a sodium current ( I Na), and a delayed rectifier potassium current ( I K_dr). The dendritic compartment contains a high-threshold calcium current ( I Ca_h), a calcium-dependent potassium current ( I K_Ca), and a current flowing into other cells through electrical coupling ( I c). First, kinetic parameters for these currents were set according to previously reported experimental data. Next, the remaining free parameters were determined to account for both static and spiking properties of single olivary neurons in vitro. We then performed a series of simulated pharmacological experiments using bifurcation analysis and extensive two-parameter searches. Consistent with previous studies, we quantitatively demonstrated the major role of I Ca_l in spiking excitability. In addition, I h had an important modulatory role in the spike generation and period of oscillations, as previously suggested by Bal and McCormick. Finally, we investigated the role of electrical coupling in two coupled spiking cells. Depending on the coupling strength, the hyperpolarization level, and the I Ca_l and I hmodulation, the coupled cells had four different synchronization modes: the cells could be in-phase, phase-shifted, or anti-phase or could exhibit a complex desynchronized spiking mode. Hence these simulation results support the counterintuitive hypothesis that electrical coupling can desynchronize coupled inferior olive cells.