bluuebunny/crossref_metadata_2025 huggingface dataset:
Anisotropic and heterogeneous diffusion in the turtle cerebellum: implications for volume transmission
Authors: Rice M. E. , Okada Y. C. , Nicholson C.
Published: December 2017

1. Measurements of extracellular diffusion properties were made in three orthogonal axes of the molecular and granular layers of the isolated turtle cerebellum with the use of iontophoresis of tetramethylammonium (TMA+) combined with ion-selective microelectrodes. 2. Diffusion in the extracellular space of the molecular layer was anisotropic, that is, there was a different value for the tortuosity factor, lambda i, associated with each axis of that layer. The x- and y-axes lay in the plane parallel to the pial surface of this lissencephalic cerebellum with the x-axis in the direction of the parallel fibers. The z-axis was perpendicular this plane. The tortuosity values were lambda x = 1.44 +/- 0.01, lambda y = 1.95 +/- 0.02, and lambda z = 1.58 +/- 0.01 (mean +/- SE). By contrast, the granular layer was isotropic with a single tortuosity value, lambda Gr = 1.77 +/- 0.01. 3. These data confirm the applicability of appropriately extended Fickian equations to describe diffusion in anisotropic porous media, including brain tissue. 4. Heterogeneity between the molecular and granular layer was revealed by a striking difference in extracellular volume fraction, alpha, for each layer. In the molecular layer alpha = 0.31 +/- 0.01, whereas in the granular layer alpha = 0.22 +/- 0.01. 5. Volume fraction and tortuosity affected the time course and amplitude of extracellular TMA+ concentration after iontophoresis. This was modeled by the use of the average parameters determined experimentally, and the nonspherical pattern of diffusion in the molecular layer was compared with the spherical distribution in the granular layer and agarose gel by computing isoconcentration ellipsoids. 6. One functional consequence of these results was demonstrated by measuring local changes in [K+]o and [Ca2+]o after microiontophoresis of a cerebellar transmitter, glutamate. The ratios of ion shifts in the x- and y-axes in the granular layer were close to unity, with a ratio of 1.04 +/- 0.08 for the rise in [K+]o and 1.03 +/- 0.17 for the decrease in [Ca2+]o. In contrast, ion shifts in the molecular layer had an x:y ratio of 1.44 +/- 0.14 for the rise in [K+]o and 2.10 +/- 0.42 for the decrease in [Ca2+]o. 7. These data demonstrate that the structure of cellular aggregates can channel the migration of substances in the extracellular microenvironment, and this could be a mechanism for volume transmission of chemical signals. For example, the preferred diffusion direction of glutamate along the parallel fibers would help constrain an incoming excitatory stimulus to stay "on-beam."
Excitatory amino acid neurotransmission at sensory-motor and interneuronal synapses of Aplysia californica.
Authors: Trudeau Louis-Eric , Castellucci Vincent F.
Published: December 2017

Pages 1221–1230: Louis-Eric Trudeau and Vincent F. Castellucci, “Excitatory amino acid neurotransmission at sensory-motor and interneuronal synapses of Aplysia californica.” Page 1225, Fig. 4, should have appeared as follows:

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An examination of frog myelinated axons using intracellular microelectrode recording: the role of voltage-dependent and leak conductances on the steady-state electrical properties
Authors: Poulter M. O. , Hashiguchi T. , Padjen A. L.
Published: December 2017

1. Intracellular microelectrode current-clamp technique was used to study the steady-state membrane properties of single intact large primary afferent axons (conduction velocity > 10 m/s) attached to isolated hemisected frog spinal cord. 2. Hyperpolarizing electrotonic potentials (ETPs) had a slow complex multiphasic charging. This complex charging could be approximated by two time constants: one in the range of 70–210 ms, the other of < 20 ms. 3. Two regions of outward and inward rectification hyperpolarized to the resting membrane potential were observed, in addition to the previously characterized outward rectification active at potentials depolarized to resting membrane potential. The peak and steady-state input resistance of these axons in tetrodotoxin Ringer solution was on average 65.6 +/- 21.1 and 31.1 +/- 10.8 M omega, mean +/- SE, respectively. 4. Application of external tetraethylammonium (10–20 mM) significantly depolarized the axon and decreased the outward rectification just hyperpolarized to the resting membrane potential. This outward rectification could also be blocked by external barium ions (2–10 mM). 5. Activation of an inward or anomalous rectification in these axons was observed 300–600 ms after the start of a current pulse. In addition, a depolarizing afterpotential (DAP) (1–3 mV in amplitude, 500 ms-10 s in duration) was evident after a current pulse in which inward rectification had been activated. This DAP most likely reflected the slow inactivation of the inwardly rectifying conductance. 6. Inward rectification was blocked by external application of cesium ions (1–3 mM) but it was insensitive to external application of barium ions (2–10 mM). The blockade of the voltage attenuation was accompanied by a disappearance of the DAP and an increase in the charging time constant of the axon. This blockade resulted in a single linear voltage-current (V-I) relationship. Axons now had, on average, an input resistance of 114 +/- 19.1 M omega. 7. Reducing the concentration of external potassium ions increased both the peak and steady-state slope resistance. Reducing the external sodium concentration altered the ETPs and the V-I relationship little but it consistently reduced the magnitude and length of the DAP. These results are compatible with the hypothesis that anomalous rectification is a mixed ionic conductance dependent on potassium and sodium ions in the external media. 8. Overall, the V-I relationship of these intact axons had both linear and nonlinear regions reflecting the activity of numerous slowly activating and inactivating conductances. (ABSTRACT TRUNCATED AT 400 WORDS)
Sweet taste transduction in hamster taste cells: evidence for the role of cyclic nucleotides
Authors: Cummings T. A. , Powell J. , Kinnamon S. C.
Published: December 2017

1. Physiological and behavioral responses to artificial sweeteners, natural sweeteners, and cyclic nucleotides were assessed using two techniques. An extracellular “in situ” technique recorded action potentials from fungiform taste buds and the two-bottle preference test measured behavioral preferences for the different sweeteners. 2. Two high-potency sweeteners, NC-00274-01 (NC01) and NC-00044-AA (NCAA), were preferred over water at micromolar concentrations. Saccharin and sucrose were likewise preferred, but at millimolar concentrations. 3. Bursts of action currents were elicited by sucrose at 200 mM, saccharin at 20 mM, and NCAA at 0.1 mM. A concentration-response curve for the high-potency sweetener NC01 revealed a threshold concentration of 1 microM and a saturation concentration of 100 microM. No responses were elicited by aspartame. 4. The responses to different sweeteners adapted rapidly at saturating concentrations. With NC01, adaptation was concentration dependent: at threshold the response adapted very slowly if at all. Adaptation increased with increasing concentration. 5. Membrane-permeant analogues of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate mimicked sweeteners in their ability to elicit a response. This occurred with high fidelity: nearly every taste bud that responded to sweeteners also responded to the nucleotides and every sweet-unresponsive taste bud was nucleotide unresponsive. 6. The sweet responses and nucleotide responses occurred in the absence of permeant apical cations and were not enhanced nor diminished by the presence of such cations. Amiloride had no effect on the sweet response.
Nitric oxide mediates ongoing discharges in dorsal root ganglion cells after peripheral nerve injury
Authors: Wiesenfeld-Hallin Z. , Hao J. X. , Xu X. J. , Hokfelt T.
Published: December 2017

1. We have examined the effect of intravenously injected nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide (NO) synthase, on the ongoing discharges originating in dorsal root ganglia in rats. 2. Ongoing activity was recorded from dorsal rootlets that were responsive to electrical stimulation of the axotomized sciatic nerve. Resection of the nerve proximal to the neuroma did not appreciably influence the rate of ongoing activity. Intravenous L-NAME (100 and 200 mumol/kg) suppressed ongoing activity both when the neuroma was intact or acutely resected. The effect of L-NAME was reversed by L-arginine (575 and 1,150 mumol/kg). 3. L-NAME had no effect on ongoing activity recorded from dorsal rootlets in normal rats or rootlets with no sciatic input in axotomized rats. 4. No ongoing activity could be recorded from sciatic nerve filaments that had been sectioned proximally before the recording in axotomized rats, although a response could be elicited by mechanical stimulation of the neuroma. 5. Because peripheral axotomy has been shown to markedly increase the level of mRNA for NO synthase in dorsal root ganglion cells, the present results indicate that NO may be involved in the generation of spontaneous discharges in deafferentated dorsal root ganglia.
Significance of conductances in Hodgkin-Huxley models
Authors: Foster W. R. , Ungar L. H. , Schwaber J. S.
Published: December 2017

1. We explore the roles of conductances in Hodgkin-Huxley (HH) models using a method that allows the explicit linking of HH model input-output behavior to parameter values for maximal conductances, voltage shifts, and time constants. The procedure can be used to identify not only the parameter values most critical to supporting a neuronal activity pattern of interest but also the relationships between parameters which may be required, e.g., limited ranges of relative magnitudes. 2. The method is the repeated use of stochastic search to find hundreds or even thousands of different sets of model parameter values that allow a HH model to produce a desired behavior, such as current-frequency transduction, to within a desired tolerance, e.g., frequency match to within 10 Hz. Graphical or other analysis may then be performed to reveal the shape and boundaries of the parameter solution regions that support the desired behavior. 3. The shape of these parameter regions can reveal parameter values and relationships essential to the behavior. For instance, graphical display may reveal covariances between maximal conductance values, or a much wider range of variation in some maximal conductance values than in others. 4. We demonstrate the use of these techniques with simple, representative HH models, primarily that of Connor et al. for crustacean walking leg axons, but also some extensions of the results are explored using the more complex model of McCormick and Huguenard for thalamocortical relay neurons. Both models are single compartment. Behaviors studied include current-to-frequency transduction, the time delay to first action potential in response to current steps, and the timing of action potential occurrences in response to both square-wave current injection and the injection of currents derived from in vitro records of excitatory postsynaptic currents. 5. Using these simple models, we find that relatively general behaviors such as current-frequency (I/F) curves may be supported by very broad, but bounded parameter solution regions, with the shape of the solution regions revealing the relative importance of the maximal conductances of a model in creating the behavior. Furthermore, we find that a focus on increasingly specific behaviors, such as I/F behavior, defined by tolerances of only a few hertz combined with strict requirements for action potential height, inevitably leads to increasingly narrow, and eventually nonphysiologically narrow, regions of acceptable parameter values. 6. We use the Connor et al. model to reproduce the in vitro action potential timing responses of a rat brain stem neuron to various stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
GABAB receptor activation causes a depression of low- and high-voltage-activated Ca2+ currents, postinhibitory rebound, and postspike afterhyperpolarization in lamprey neurons
Authors: Matsushima T. , Tegner J. , Hill R. H. , Grillner S.
Published: December 2017

1. Activation of gamma-aminobutyric acid-B (GABAB) receptors during N-methyl-D-aspartate (NMDA)-induced fictive locomotor activity in the lamprey spinal cord reduces the burst frequency and changes the intersegmental coordination. Presynaptic inhibition of both the excitatory and inhibitory synaptic transmission from spinal premotor interneurons occurs through GABAB receptor activation. To further analyze the cellular mechanisms underlying the GABABergic modulation of the locomotor network, the present study investigates somatodendritic effects of GABAB receptor activation on interneurons and motoneurons in the lamprey spinal cord in vitro using single-electrode current- and voltage-clamp techniques. 2. High- (HVA) and low- (LVA) voltage-activated calcium currents were studied with single-electrode voltage clamp when Na+ and K+ currents were blocked--using tetrodotoxin, tetraethylammonium (TEA), and CsCl electrodes--after substituting Ca2+ with Ba2+. Cobalt-sensitive inward barium currents, activated at -50 mV, became larger when the holding potential was set to a more hyperpolarized level, thus suggesting the existence of an LVA calcium current. The presence of cobalt-sensitive inward barium currents activated at -30 and -10 mV suggests the existence of an HVA calcium current. GABAB receptor activation (baclofen) reduced the peak amplitude of both the LVA and HVA Ca2+ component. 3. The late phase of the afterhyperpolarization (AHP), which follows the action potential, was reduced in amplitude by cobalt, thus lending further support to the notion that the Ca2+ influx, and the subsequent activation of Ca(2+)-dependent K+ channels (KCa2+), constitutes the major part of the AHP generation. Application of the GABAB agonist baclofen also reduced the peak amplitude of the AHP in interneurons and motoneurons, and this reduction was counteracted by the GABAB antagonist 2(OH)saclofen. Baclofen reduced the duration of action potentials broadened by TEA, thus suggesting that the Ca2+ inflow was reduced. Intracellular injection of the GTP analogue GTP gamma S also reduced the duration of the action potential and the peak amplitude of the AHP in TEA, thus supporting the notion that a GTP-binding protein (G-protein)-mediated GABAB receptor activation reduced the calcium inflow, leading to less activation of KCa channels and, consequently, to a smaller peak amplitude of the AHP. 4. Baclofen suppressed the subthreshold depolarization induced by a depolarizing current pulse injection without affecting either the spike threshold or the resting membrane conductance.(ABSTRACT TRUNCATED AT 400 WORDS)
A separate local pattern-generating circuit controls the movements of each swimmeret in crayfish
Authors: Murchison D. , Chrachri A. , Mulloney B.
Published: December 2017

1. Within an abdominal segment, the motor output from the segmental ganglion to the swimmerets consists of coordinated bursts of impulses in the separate pools of motor neurons innervating the left and right limbs. This coordinated motor pattern features alternating (out-of-phase) bursts of impulses in the power-stroke (PS) and return-stroke (RS) motor axons that innervate each swimmeret. PS bursts on both sides of each segment occur simultaneously (in-phase), and so RS bursts on both sides are also in-phase. 2. With all intersegmental connections interrupted, isolated abdominal ganglia were able to sustain the normal swimmeret motor pattern of alternating PS/RS activity that was bilaterally in-phase. 3. After an isolated ganglion was surgically bisected down the midline, the isolated hemiganglia that resulted could produce stable, coordinated alternation of PS and RS bursts. 4. The neuropeptide proctolin could induce rhythmic oscillations of membrane potential in swimmeret neurons when spiking was blocked by tetrodotoxin (TTX). For neurons within the same hemiganglion, these oscillations retained the same phase relations they displayed in controls, but the oscillations of neurons in different hemiganglia became uncoordinated. 5. Synaptic transmission between swimmeret neurons in the same hemiganglion persisted in the presence of TTX. Swimmeret interneurons that could activate the pattern-generating circuitry under control conditions could induce membrane-potential oscillations in swimmeret neurons of the same hemiganglion when TTX was present. 6. We conclude that a separate hemisegmental pattern-generating circuit controls the rhythmic PS and RS movements of each swimmeret. Each circuit is located in the same hemiganglion as the population of motor neurons that innervates the local swimmeret. Graded transmission is sufficient to coordinate the timing of oscillatory activity within the hemisegmental circuitry. These hemisegmental circuits are coupled by intersegmental and bilateral coordinating pathways that are dependent on sodium action potentials for their operation.
Gaze-related activity of putative inhibitory burst neurons in the head-free cat
Authors: Cullen K. E. , Guitton D. , Rey C. G. , Jiang W.
Published: December 2017

1. Previous studies in the cat have demonstrated that output neurons of the superior collicular as well as brain stem omnipause neurons have discharges that are best correlated, not with the trajectory of the eye in the head but, with the trajectory of the visual axis in space (gaze = eye-in-head + head-in-space) during rapid orienting coordinated eye and head movements. In this study, we describe the gaze-related activity of cat premotor “inhibitory burst neurons”(IBNs) identified on the basis of their position relative to the abducens nucleus. 2. The firing behavior of IBNs was studied during 1) saccades made with the head stationary, 2) active orienting combined eye-head gaze shifts, and 3) passive movements of the head on the body. IBN discharges were well correlated with the duration and amplitude of saccades made when the head was stationary. In both head-free paradigms, the behavior of cat IBNs differed from that of previously described primate “saccade bursters”. The duration of their burst was better correlated with gaze than saccade duration, and the total number of spikes in a burst was well correlated with gaze amplitude and generally poorly correlated with saccade amplitude. The behavior of cat IBNs also differed from that of previously described primate “gaze bursters”. The slope of the relationship between the total number of spikes and gaze amplitude observed during head-free gaze shifts was significantly lower than that observed during head-fixed saccades. 3. These studies suggest that cat IBNs do not fit into the categories of gaze-bursters or saccade-bursters that have been described in primate studies.(ABSTRACT TRUNCATED AT 250 WORDS)
(RS)-alpha-methyl-4-carboxyphenylglycine neither prevents induction of LTP nor antagonizes metabotropic glutamate receptors in CA1 hippocampal neurons
Authors: Chinestra P. , Aniksztejn L. , Diabira D. , Ben-Ari Y.
Published: December 2017

1. The effects of the putative antagonist of metabotropic glutamate receptors (mGluR), (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), were investigated in CA1 hippocampal neurons using intracellular and extracellular recordings. 2. MCPG (0.5 mM) did not antagonize the characteristic block of the slow afterhyperpolarization and spike accomodation produced by the selective mGluR agonist, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (30 microM). 3. MCPG (0.5 mM) did not prevent the inward current produced by 1S,3R-ACPD (30 microM) [240 +/- 14 and 255 +/- 21 pA (mean +/- SD) in the absence and in presence of MCPG, respectively]. 4. MCPG (0.5 mM, 10 min) did not prevent the presynaptically mediated reduction by 1S,3R-ACPD (50 microM, 10 min) of the field excitatory postsynaptic potential (EPSP) (51 +/- 7 and 64 +/- 10% in the absence and in presence of MCPG, respectively). 5. MCPG (0.5 mM) did not prevent the induction of long-term potentiation by a high-frequency tetanic stimulation of Schaffer collaterals (100 Hz, 1 s) (+61 +/- 5 and +67 +/- 16% increase in the absence and presence of MCPG, respectively). 6. These observations suggest that MCPG is not an antagonist of the subtypes of mGlu receptors that are present in CA1 pyramidal neuron. Possible selectivity of this compound for specific mGluRs is discussed in view of the regional distribution of metabotropic receptors in the hippocampus.
Electrophysiological properties of guinea pig trigeminal motoneurons recorded in vitro
Authors: Chandler S. H. , Hsaio C. F. , Inoue T. , Goldberg L. J.
Published: December 2017

1. Intracellular recording and stimulation were made from guinea pig trigeminal motoneurons (TMNs) in brain stem slices. Electrophysiological properties were examined and the underlying currents responsible for motoneuron excitability were investigated by the use of current clamp and single electrode voltage clamp (SEVC) techniques. 2. The voltage responses to subthreshold hyperpolarizing or depolarizing current pulses showed voltage- and time-dependent inward rectification. SEVC analysis demonstrated that the hyperpolarizing inward rectification resulted from the development of a slowly occurring voltage-dependent inward current activated at hyperpolarized membrane potentials. This current persisted in solutions containing low Ca2+/Mn2+, tetraethylammonium (TEA), and Ba2+, whereas it was reduced by 1–3 mM cesium. The depolarizing inward rectification was mediated by a persistent sodium current (INa-P) that was completely abolished by bath application of tetrodotoxin (TTX). 3. Action potential characteristics were studied by intracellular stimulation with brief current pulses (< 3 ms) in combination with ionic substitutions or application of specific ionic conductance blocking agents. Bath application of TTX abolished the action potential, whereas 1–10 mM TEA or 0.5–2 mM 4-aminopyridine (4-AP) increased, significantly, the spike duration, suggesting participation of the delayed rectifier and A-current type conductances in spike repolarization. SEVC analysis revealed a TEA-sensitive sustained outward current and a fast, voltage-dependent, transient current with properties consistent with their roles in spike repolarization. 4. TMN afterhyperpolarizing potentials (AHPs) that followed a single spike consisted of fast and slow components usually separated by a depolarizing hump [afterdepolarization (ADP)]. The fast component was abolished by TEA or 4-AP but not by Mn2+, Co2+, or the bee venom apamin. In contrast, the slow AHP was readily reduced by Mn2+, Co2+, or apamin, suggesting participation of an apamin-sensitive, calcium-dependent K+ conductance in the production of the slow AHP. SEVC analysis and ionic substitutions demonstrated a slowly activating and deactivating calcium-dependent K+ current with properties that could account for the slow AHP observed in these neurons. 5. Repetitive discharge was examined with long depolarizing current pulses (1 s) and analysis of frequency-current plots. When evoked from resting potential (about -55 mV), spike onset from rheobase occurred rapidly and was maintained throughout the current pulse. At higher current intensities, early and late adaptations in spike discharge were observed. Frequency-current plots exhibited a bilinear relationship for the first interspike interval (ISI) in approximately 50% of the neurons tested and in most neurons tested during steady-state discharge (SS).(ABSTRACT TRUNCATED AT 400 WORDS)
Modulatory influence of putative inhibitors of nitric oxide synthesis on visual processing in the cat lateral geniculate nucleus
Authors: Cudeiro J. , Rivadulla C. , Rodriguez R. , Martinez-Conde S. , Acuna C. , Alonso J. M.
Published: December 2017

1. Using an in vivo preparation we have examined the actions of two inhibitors of nitric oxide synthase (NOS), NG-nitro-L-arginine (L-NOArg) and NG-methyl-L-arginine (L-MeArg), in the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses obtained to iontophoretic application of these substances during visual stimulation with those elicited by visual stimulation alone. The effects of concurrent ejection of L-arginine (L-Arg), the normal physiological substrate of NOS, and D-arginine, the inactive isomer, were tested on these responses. 2. Extracellular application of L-NOArg and L-MeArg produced clear and repeatable effects, consisting of substantial reduction in discharge rate without affecting response selectivity, on 94% of tested cells. These effects were prevented by simultaneous application of L-Arg, which when ejected alone produced no change on visual evoked responses. 3. The data suggest that nitric oxide (NO) is necessary for the transmission of the visual input under normal visual stimulation and show a direct involvement of NO in visual information processing at the level of dLGN, suggesting that its contribution to brain mechanisms is more profound than previously thought.
Neonatal irradiation prevents the formation of hippocampal mossy fibers and the epileptic action of kainate on rat CA3 pyramidal neurons
Authors: Gaiarsa J. L. , Zagrean L. , Ben-Ari Y.
Published: December 2017

1. The effects of unilateral gamma-ray irradiation at birth on the properties of adult CA3 pyramidal neurons have been studied in hippocampal slices. 2. Neonatal gamma-ray irradiation reduced by 80% the number of granule cells and prevented the formation of mossy fiber synapses without reducing the number of CA3 pyramidal cells. The destruction of the mossy fibers was also confirmed with extracellular recordings. 3. Excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) evoked by stimulation of the stratum radiatum had similar properties in nonirradiated and irradiated hippocampi: the EPSP reversed polarity near 0 mV, was reduced in amplitude by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)-2-amino-5-phosphonovalerate (APV, 50 microM); the fast and slow IPSPs reversed at -75 and -100 mV, were blocked by bicuculline (10 microM), and reduced by phaclofen (0.5 mM), respectively. 4. Bath application of kainate (300–500 nM) evoked epileptiform activity in 81.5% of nonirradiated hippocampal CA3 regions and only in 29% of the irradiated CA3 regions. In contrast, bath application of high potassium (7 mM) and bicuculline (10 microM) generated spontaneous and evoked epileptiform activity in both nonirradiated and irradiated CA3 regions. 5. In nonirradiated and irradiated CA3 regions, kainate (200–300 nM) reduced the amplitude of the fast and slow IPSPs, reduced spike accommodation, and increased the duration of the action potential generated by a depolarizing pulse. 6. The postsynaptic responses of CA3 neurons to bath application of glutamatergic agonists were similar in nonirradiated and irradiated hippocampi in terms of amplitude, reversal potential, and pharmacology. 7. It is concluded that the most conspicuous effect of neonatal gamma-ray irradiation is to prevent the epileptic action of kainate. We propose that kainate generates epileptiform activity in the intact CA3 region by activating high-affinity binding sites located on the mossy fiber terminals.
Correlating resting discharge with small signal sensitivity and discharge variability in primary endings of cat soleus muscle spindles
Authors: Scott J. J. , Gregory J. E. , Proske U. , Morgan D. L.
Published: December 2017

1. In a previous report we proposed that primary endings of cat soleus muscle spindles can be separated into two kinds. One kind, called by us silent endings, at muscle lengths shorter than Lm -10 (maximum body length -10 mm), fell silent after a 5 mm shortening step. Spontaneous endings, on the other hand, were able to resume a resting discharge after a brief pause at all muscle lengths down to Lm -20. This report examines further differences between the two kinds of endings. 2. There were consistent differences in the muscle length dependence of the maintained level of resting discharge of the two kinds of endings, measured after a conditioning contraction or a contraction followed by a shortening step. The resting discharge of spindles with spontaneous endings, after both forms of conditioning increased progressively with length. For silent endings, after a conditioning contraction, resting discharge fell slightly at longer lengths. 3. Discharge variability, measured at a number of muscle lengths, showed a dependence both on mean interimpulse interval and on spindle type, being higher in silent than spontaneous spindles. 4. Small signal sensitivity was measured with the use of 1 Hz sinusoidal stretches applied longitudinally to the tendon. Sine wave amplitude was adjusted to give a 30% depth of modulation of the resting discharge. Spontaneous endings were consistently less sensitive to the stretches than silent endings at all muscle lengths. Average sensitivities, measured over a range of lengths between Lm -4 and Lm -20 mm were 0.30 imp.s-1.microns -1 for spontaneous endings and 0.66 imp.s-1.microns -1 for silent endings.(ABSTRACT TRUNCATED AT 250 WORDS)
An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses
Authors: De Schutter E. , Bower J. M.
Published: December 2017

1. Both excitatory and inhibitory postsynaptic channels were added to a previously described complex compartmental model of a cerebellar Purkinje cell to examine model responses to synaptic inputs. All model parameters remained as described previously, leaving maximum synaptic conductance as the only parameter that was tuned in the studies described in this paper. Under these conditions the model was capable of reproducing physiological recorded responses to each of the major types of synaptic input. 2. When excitatory synapses were activated on the smooth dendrites of the model, the model generated a complex dendritic Ca2+ spike similar to that generated by climbing fiber inputs. Examination of the model showed that activation of P-type Ca2+ channels in both the smooth and spiny dendrites augmented the depolarization during the complex spike and that Ca(2+)-activated K+ channels in the same dendritic regions determined the duration of the spike. When these synapses were activated under simulated current-clamp conditions the model also generated the characteristic dual reversal potential of the complex spike. The shape of the dendritic complex spike could be altered by changing the maximum conductance of the climbing fiber synapse and thus the amount of Ca2+ entering the cell. 3. To explore the background simple spike firing properties of Purkinje cells in vivo we added excitatory “parallel fiber” synapses to the spiny dendritic branches of the model. Continuous asynchronous activation of these granule cell synapses resulted in the generation of spontaneous sodium spikes. However, very low asynchronous input frequencies produced a highly regular, very fast rhythm (80–120 Hz), whereas slightly higher input frequencies resulted in Purkinje cell bursting. Both types of activity are uncharacteristic of in vivo Purkinje cell recordings. 4. Inhibitory synapses of the sort presumably generated by stellate cells were also added to the dendritic tree. When asynchronous activation of these inhibitory synapses was combined with continuous asynchronous excitatory input the model generated somatic action potentials in a much more stochastic pattern typical of real Purkinje cells. Under these conditions simulated inter-spike interval distributions resembled those found in experimental recordings. Also, as with in vivo recordings, the model did not generate dendritic bursts. This was mainly due to inhibition that suppressed the generation of dendritic Ca2+ spikes. 5. In the presence of asynchronous inhibition, changes in the average frequency of excitatory inputs modulated background simple spike firing frequencies in the natural range of Purkinje cell firing frequencies (30–100 Hz). This modulation was very sensitive to small changes in the average frequency of excitatory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)
Neural encoding of single-formant stimuli in the cat. II. Responses of anteroventral cochlear nucleus units
Authors: Wang X. , Sachs M. B.
Published: December 2017

1. We have studied responses of anteroventral cochlear nucleus (AVCN) units to single-formant stimuli (SFS), in an effort to make quantitative comparisons with responses observed in auditory-nerve fibers (ANFs) to the same stimuli (Wang and Sachs 1993) and to reveal some of the signal processing mechanisms at the AVCN. Single-unit recordings and subsequent analyses were performed on each type of commonly recorded units, namely primarylike (Pri), primarylike with notch (PN), sustained chopper (ChS), transient chopper (ChT), and onset chopper (OnC), as well as a few onset (On) units, from the AVCN in anesthetized cats. The responses were obtained at a wide range of sound levels and at a frequency range of 1-10 kHz. Modulation in the envelopes of discharge patterns was quantified by a measure called modulation depth. 2. At moderate to high sound levels, most AVCN units were found to have enhanced modulation depth compared with that of ANFs, although the degree of enhancement varies among different types. All AVCN units, except Pri type, showed an enhancement in modulation depth over that of the highest of ANFs at moderate to high sound levels in the order of (from the highest to the lowest) On, OnC, ChT/PN, and ChS. Specifically, 1) modulation depth in Pri units was comparable to that of high spontaneous rate (SR) ANFs at low sound levels and to that of low/medium SR ANFs at high sound levels (in dB SPL). When sound level was normalized by unit threshold, Pri units, on average, exhibited only limited enhancement in envelope modulation at high sound levels (> 80 dB re threshold); 2) PN units showed substantially enhanced modulation depth over that of all SR groups of ANFs at moderate to high sound levels in dB SPL or dB re threshold scales; 3) significant enhancement in modulation depth was seen in both ChS and ChT units, with a slightly higher modulation depth in ChT type across sound levels (in dB SPL or dB re threshold); 4) modulation depth of OnC units was higher than those of primary-like (Pri and PN) and chopper (ChS and ChT) units at a wide range of sound levels; 5) responses from a limited sample of On units showed the highest modulation depth among all types of AVCN units. 3. Detailed analysis revealed that the enhanced modulation depth in the responses of AVCN units is the result of increased envelope peak height and decreased envelope minimum, relative to those of ANFs.(ABSTRACT TRUNCATED AT 400 WORDS)
Efferent neurons and suspected interneurons in motor cortex of the awake rabbit: axonal properties, sensory receptive fields, and subthreshold synaptic inputs
Authors: Swadlow H. A.
Published: December 2017

1. Properties of antidromically identified efferent neurons within the cortical representation of the vibrissae, sinus hairs, and philtrum were examined in motor cortex of fully awake adult rabbits. Efferent neurons were tested for both receptive field and axonal properties and included callosal (CC) neurons (n = 31), ipsilateral corticocortical (C-IC) neurons (n = 34) that project to primary somatosensory cortex (S-1), and corticofugal neurons of layer 5 (CF-5) (n = 33) and layer 6 (CF-6) (n = 32) that project to and/or beyond the thalamus. Appropriate collision tests demonstrated that substantial numbers of corticocortical efferent neurons project an axon to both the corpus callosum and to ipsilateral S-1. 2. Suspected interneurons (SINs, n = 37) were also studied. These neurons were not activated antidromically from any stimulus site but did respond synaptically to electrical stimulation of the ventrolateral (VL) thalamus and/or S-1 with a burst of three or more spikes at frequencies from 600 to > 900 Hz. All of these neurons also responded synaptically to stimulation of the corpus callosum. The action potentials of these neurons were much shorter in duration (mean = 0.48 ms), than those of efferent neurons (mean = 0.90 ms). 3. CF-5 neurons differed from CC, C-IC, and CF-6 neurons in their spontaneous firing rates, axonal properties, and receptive field properties. Whereas CF-5 neurons had a mean spontaneous firing rate of 4.1 spikes/s, CC, C-IC, and CF-6 neurons all had mean values of < 1 spike/s. Axonal conduction velocities of CF-5 neurons were much higher (mean = 12.76 m/s) than either CC (1.47 m/s), C-IC (0.97 m/s), or CF-6 (mean = 1.96 m/s) neurons. A decrease in antidromic latency (the "supernormal" period) followed a single prior impulse in most CC, C-IC, and CF-6 neurons but was minimal or absent in CF-5 neurons. Although all but two CF-5 neurons responded to peripheral sensory stimulation, many CC (35%), C-IC (59%), or CF-6 (66%) neurons did not. CC, CF-5, and CF-6 neurons that did not respond to sensory stimulation had significantly lower axonal conduction velocities and spontaneous firing rates than those that responded to such stimulation. 4. Sensory receptive fields of neurons in motor cortex were considerably larger than those observed in S-1 but were similar in size to those seen in secondary somatosensory cortex (S-2).(ABSTRACT TRUNCATED AT 400 WORDS)
Whole-cell analysis of ionic currents underlying the firing pattern of neurons in the gustatory zone of the nucleus tractus solitarii
Authors: Tell F. , Bradley R. M.
Published: December 2017

1. Previous work from this laboratory has shown that rostral nucleus tractus solitarii (rNTS) neurons can be separated into four different classes on the basis of responses to a current injection paradigm consisting of membrane hyperpolarization immediately followed by a depolarizing pulse. These classes have been termed Group I, II, III, and IV neurons. The regular repetitive firing discharge pattern of Group I cells is changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons delays the firing discharge induced by depolarization. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of spikes. We used whole-cell recordings and pharmacological channel blockers in an in vitro brain stem slice preparation to determine the ionic basis for the repetitive firing properties of rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input resistance and increased action potential duration in all groups of neurons. However, the discharge pattern of Group I, III, and IV neurons was either unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group II cells induced by hyperpolarization was strongly reduced and in some cases completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive conductance primarily underlies the firing pattern of Group II cells. 3. Voltage-clamp recordings revealed that the delay in Group II neurons is due to a transient outward potassium current that is partially inactivated around the resting membrane potential. Hyperpolarization removed this inactivation, causing a delay in the firing of the cell. The potassium current was blocked by 4-AP. A similar current was occasionally seen in neurons of the other groups. On the basis of its voltage and pharmacological dependence this current was presumed to be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM) saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group II neurons the delay in firing activity was increased. In the other groups the repetitive firing pattern was suppressed. In addition the amplitude of the afterhyperpolarization occurring after a short train of action potentials was substantially reduced. This indicates that calcium currents (ICa) and calcium-activated potassium currents (IKCa) contribute to the repetitive firing properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)
Lateral suppression and inhibition in the cochlear nucleus of the cat
Authors: Rhode W. S. , Greenberg S.
Published: December 2017

1. The ability of cells in the cochlear nucleus (CN) to encode frequency information in the presence of background noise on the basis of "place/rate" information was investigated by measuring the threshold, magnitude, and extent of lateral suppression in the ventral and dorsal CN of the anesthesized cat. The suppression regions were delineated through the use of "masked" response areas (MRAs). The MRA is a family of isointensity curves derived from the average discharge rate in response to a tone of variable frequency and sound pressure level in the presence of a concurrently presented broadband, quasi-flat-spectrum noise. Tonal stimuli of sufficient intensity are often effective in significantly reducing the average discharge rate of CN neurons over a wide frequency range. 2. Most units in the CN exhibit prominent lateral suppressive sidebands, but the variability in threshold, magnitude, and extent of suppression is large. Primary-like and onset units of the ventral CN manifest the least suppression and have the highest suppression thresholds. Pauser/buildup units in the dorsal division and choppers distributed throughout the CN show the largest amount of suppression and have the lowest suppression thresholds. 3. Auditory nerve fibers manifest some degree of lateral suppression, particularly fibers of low and medium spontaneous rate. However, in few instances are the threshold, magnitude, and extent comparable with that observed among the majority of chopper and pauser/buildup units. For this reason the lateral suppression observed among the latter unit types is unlikely to originate entirely from cochlear processes, but rather is likely to reflect largely neural mechanisms intrinsic to the CN. In contrast, the MRAs of most primary-like and onset units suggest that the suppression behavior of most of these cells originates mostly, if not entirely, in the cochlea and auditory nerve. 4. A primary consequence of lateral suppression is to preserve the sharp frequency selectivity of CN neurons at moderate to high sound pressure levels, particularly in background noise. In this fashion lateral suppressive mechanisms potentially enhance the representation of spectral information on the basis of place/rate information relative to that in the auditory nerve under noisy background conditions. 5. Lateral suppressive mechanisms probably underlie the dynamic range shift seen in the presence of a simultaneously presented noise. This mechanism may be crucial for preserving the ability to perceive signals in a noisy background.
Low-threshold calcium current and resonance in thalamic neurons: a model of frequency preference
Authors: Hutcheon B. , Miura R. M. , Yarom Y. , Puil E.
Published: December 2017

1. We constructed a mathematical model of the subthreshold electrical behavior of neurons in the nucleus mediodorsalis thalami (MDT) to elucidate the basis of a Ni(2+)-sensitive low-frequency (2-4 Hz) resonance found previously in these neurons. 2. A model that included the low- and high-threshold Ca2+ currents (IT and IL), a Ca(2+)-activated K+ current (IC), a rapidly inactivating K+ current (IA), a voltage-dependent K+ current which we call IKx, and a voltage-independent leak current (Il), successfully simulated the low-threshold spike observed in MDT neurons. This model (the MDT model) and a minimal version of the model containing only IT and I1 (the minimal MDT model) were used in the analysis. 3. An impedance function was derived for a linearized version of the MDT model. This showed that the model predicts a low-frequency (2-4 Hz) resonance in the voltage response to "small" oscillatory current inputs (producing voltage changes of < 10 mV) when the membrane potential is between -60 and -85 mV. 4. Further examination of the impedances for the MDT and minimal MDT models shows that IT underlies the frequency- and voltage-dependent resonance. The slow inactivation of IT results in an attenuation of voltage responses to low frequencies, resulting in a band-pass behavior. The fast activation of IT amplifies the resonance and modulates the peak frequency but does not, in itself, cause resonance. 5. When voltage responses are small (< 10 mV), the strength and voltage-dependence of resonance of the minimal MDT model are determined by the steady-state window conductance, gw, due to IT. This steady-state conductance arises where the steady-state activation, m(infinity2)(V), and inactivation, h(infinity) (V), curves overlap. Parallel shifts in the inactivation curve can eliminate or enhance resonance with little effect on the IT-dependent low-threshold spike evoked after hyperpolarizing current pulses. When the peak magnitude of gw was large, the minimal MDT model showed spontaneous oscillations at 3 Hz with amplitudes > 30 mV. 6. Large oscillatory current inputs evoked significantly nonlinear voltage responses in the minimal MDT model, but the 2- to 4-Hz frequency selectivity (predicted from the linearized impedance) remained. 7. We conclude that the properties of the low-threshold Ca2+ current, IT, are sufficient to explain the Ni(2+)-sensitive 2- to 4-Hz resonance seen in MDT neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Corrective responses to loss of ground support during walking. I. Intact cats
Authors: Gorassini M. A. , Prochazka A. , Hiebert G. W. , Gauthier M. J.
Published: December 2017

1. In the cat step cycle the electromyographic (EMG) activity in ankle extensor muscles commences approximately 70 ms before foot contact. There is a sharp peak between 10 and 25 ms after contact and the EMG then declines for the remainder of the stance phase. It has been posited that the abrupt transition in EMG after contact is the consequence of reflexes elicited by the large barrage of afferent input that signals foot touchdown. However, it is also possible that the basic profile might be generated within the CNS, with little modification by afferent input. 2. These ideas were tested in 11 normal cats. We compared EMG responses and hindlimb kinematics in steps with normal ground support and steps in which an actuator-controlled trap door unexpectedly opened, withdrawing ground support just before foot contact. 3. In the absence of ground support the transition in EMG activity was still present. The averaged EMG pattern was similar for at least 30 ms after the foot passed through the plane of the floor. We conclude that the basic extensor activation profile in this part of the cycle is generated centrally and is not substantially altered by afferent input. 4. Between 35 and 200 ms after contact the stance phase was aborted and the foot was lifted smartly out of the hole. This reaction varied both in latency and kinematic detail, suggesting a fairly complex corrective response.(ABSTRACT TRUNCATED AT 250 WORDS)