bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Changes of Potassium Currents in CA1 Pyramidal Neurons After Transient Forebrain Ischemia
Authors: Chi Xian Xuan , Xu Zao C.
Published: December 2017

CA1 pyramidal neurons are highly vulnerable to transient cerebral ischemia. In vivo studies have shown that the excitability of CA1 neurons progressively decreased following reperfusion. To reveal the mechanisms underlying the postischemic excitability change, total potassium current, transient potassium current, and delayed rectifier potassium current in CA1 neurons were studied in hippocampal slices prepared before ischemia and at different time points following reperfusion. Consistent with previous in vivo studies, the excitability of CA1 neurons decreased in brain slices prepared at 14 h following transient forebrain ischemia. The amplitude of total potassium current in CA1 neurons increased ∼30% following reperfusion. The steady-state activation curve of total potassium current progressively shifted in the hyperpolarizing direction with a transient recovery at 18 h after ischemia. For transient potassium current, the amplitude was transiently increased ∼30% at ∼12 h after reperfusion and returned to control levels at later time points. The steady-state activation curve also shifted ∼20 mV in the hyperpolarizing direction, and the time constant of removal of inactivation markedly increased at 12 h after reperfusion. For delayed rectifier potassium current, the amplitude significantly increased and the steady-state activation curve shifted in the hyperpolarizing direction at 36 h after reperfusion. No significant change in inactivation kinetics was observed in the above potassium currents following reperfusion. The present study demonstrates the differential changes of potassium currents in CA1 neurons after reperfusion. The increase of transient potassium current in the early phase of reperfusion may be responsible for the decrease of excitability, while the increase of delayed rectifier potassium current in the late phase of reperfusion may be associated with the postischemic cell death.
Biophysical Characterization of Rat Caudal Hypothalamic Neurons: Calcium Channel Contribution to Excitability
Authors: Fan Yi-Ping , Horn Eric M. , Waldrop Tony G.
Published: December 2017

Neurons in the caudal hypothalamus (CH) are responsible for the modulation of various processes including respiratory and cardiovascular output. Previous results from this and other laboratories have demonstrated in vivo that these neurons have firing rhythms matched to the respiratory and cardiovascular cycles. The goal of the present study was to characterize the biophysical properties of neurons in the CH with particular emphasis in those properties responsible for rhythmic firing behavior. Whole cell, patch-clamped CH neurons displayed a resting membrane potential of −58.0 ± 1.1 mV and an input resistance of 319.3 ± 16.6 MΩ when recorded in current-clamp mode in an in vitro brain slice preparation. A large proportion of these neurons displayed postinhibitory rebound (PIR) that was dependent on the duration and magnitude of hyperpolarizing current as well as the resting membrane potential of the cell. Furthermore these neurons discharged tonically in response to a depolarizing current pulse at a depolarized resting membrane potential (more positive than −65 mV) but switched to a rapid burst of firing to the same stimulus when the resting membrane potential was lowered. The PIR observed in these neurons was calcium dependent as demonstrated by the ability to block its amplitude by perfusion of Ca2+-free bath solution or by application of Ni2+(0.3–0.5 mM) or nifedipine (10 μM). These properties suggest that low-voltage-activated (LVA) calcium current is involved in the PIR and bursting firing of these CH neurons. In addition, high-voltage-activated calcium responses were detected after blockade of outward potassium current or in Ba2+-replacement solution. In addition, almost all of the CH neurons studied showed spike frequency adaptation that was decreased following Ca2+removal, indicating the involvement of Ca2+-dependent K+current ( IK,Ca) in these cells. In conclusion, CH neurons have at least two different types of calcium currents that contribute to their excitability; the dominant current is the LVA or T-type. This LVA current appears to play a significant role in the bursting characteristics that may underlie the rhythmic firing of CH neurons.
Groups II and III Metabotropic Glutamate Receptors Differentially Modulate Brief and Prolonged Nociception in Primate STT Cells
Authors: Neugebauer Volker , Chen Ping-Sun , Willis William D.
Published: December 2017

The heterogeneous family of G-protein-coupled metabotropic glutamate receptors (mGluRs) provides excitatory and inhibitory controls of synaptic transmission and neuronal excitability in the nervous system. Eight mGluR subtypes have been cloned and are classified in three subgroups. Group I mGluRs can stimulate phosphoinositide hydrolysis and activate protein kinase C whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) mGluRs share the ability to inhibit cAMP formation. The present study examined the roles of groups II and III mGluRs in the processing of brief nociceptive information and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 11 anesthetized male monkeys ( Macaca fascicularis), extracellular recordings were made from 21 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (brush), marginally and distinctly noxious (press and pinch, respectively) intensity were recorded before, during, and after the infusion of group II and group III mGluR agonists into the dorsal horn by microdialysis. Different concentrations were applied for at least 20 min each (at 5 μl/min) to obtain cumulative concentration-response relationships. Values in this paper refer to the drug concentrations in the microdialysis fibers; actual concentrations in the tissue are about three orders of magnitude lower. The agonists were also applied at 10–25 min after intradermal capsaicin injection. The group II agonists (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (LCCG1, 1 μM-10 mM, n = 6) and (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268; 1 μM-10 mM, n = 6) had no significant effects on the responses to brief cutaneous mechanical stimuli (brush, press, pinch) or on ongoing background activity. In contrast, the group III agonist L(+)-2-amino-4-phosphonobutyric acid (LAP4, 0.1 μM-10 mM, n = 6) inhibited the responses to cutaneous mechanical stimuli in a concentration-dependent manner, having a stronger effect on brush responses than on responses to press and pinch. LAP4 did not change background discharges significantly. Intradermal injections of capsaicin increased ongoing background activity and sensitized the STT cells to cutaneous mechanical stimuli (ongoing activity > brush > press > pinch). When given as posttreatment, the group II agonists LCCG1 (100 μM, n = 5) and LY379268 (100 μM, n = 6) and the group III agonist LAP4 (100 μM, n = 6) reversed the capsaicin-induced sensitization. After washout of the agonists, the central sensitization resumed. Our data suggest that, while activation of both group II and group III mGluRs can reverse capsaicin-induced central sensitization, it is the actions of group II mGluRs in particular that undergo significant functional changes during central sensitization because they modulate responses of sensitized STT cells but have no effect under control conditions.
Computer Model for Action Potential Propagation Through Branch Point in Myelinated Nerves
Authors: Zhou Lei , Chiu Shing Yan
Published: December 2017

A mathematical model is developed for simulation of action potential propagation through a single branch point of a myelinated nerve fiber with a parent branch bifurcating into two identical daughter branches. This model is based on a previously published multi-layer compartmental model for single unbranched myelinated nerve fibers. Essential modifications were made to couple both daughter branches to the parent branch. There are two major features in this model. First, the model could incorporate detailed geometrical parameters for the myelin sheath and the axon, accomplished by dividing both structures into many segments. Second, each segment has two layers, the myelin sheath and the axonal membrane, allowing voltages of intra-axonal space and periaxonal space to be calculated separately. In this model, K ion concentration in the periaxonal space is dynamically linked to the activity of axonal fast K channels underneath the myelin in the paranodal region. Our model demonstrates that the branch point acts like a low-pass filter, blocking high-frequency transmission from the parent to the daughter branches. Theoretical analysis showed that the cutoff frequency for transmission through the branch point is determined by temperature, local K ion accumulation, width of the periaxonal space, and internodal lengths at the vicinity of the branch point. Our result is consistent with empirical findings of irregular spacing of nodes of Ranvier at axon abors, suggesting that branch points of myelinated axons play important roles in signal integration in an axonal tree.
Selective Expression of Electrical Correlates of Differential Appetitive Classical Conditioning in a Feeding Network
Authors: Jones Nick , Kemenes György , Benjamin Paul R.
Published: December 2017

Electrical correlates of differential appetitive classical conditioning were recorded in the neural network that underlies feeding in the snail Lymnaea stagnalis. In spaced training (15 trials over 3 days), the lips and the tentacle were used as CS+ (reinforced conditioned stimulus) or CS− (nonreinforced conditioned stimulus) sites for behavioral tactile conditioning. In one group of experimental animals, touch to the lips (the CS+ site) was followed by sucrose (the unconditioned stimulus, US), but touch to the tentacle (the CS− site) was not reinforced. In a second experimental group the CS+/CS− sites were reversed. Semi-intact lip-tentacle-CNS preparations were made from both experimental groups and a naive control group. Intracellular recordings were made from the B3 motor neuron of the feeding network, which allowed the monitoring of activity in the feeding central pattern generator (CPG) interneurons as well as early synaptic inputs evoked by the touch stimulus. Following successful behavioral conditioning, the touch stimulus evoked CPG-driven fictive feeding activity at the CS+ but not the CS− sites in both experimental groups. Naive snails/preparations showed no touch responses. A weak asymmetrical stimulus generalization of conditioned feeding was not retained at the electrophysiological level. An early excitatory postsynaptic potential (EPSP) response to touch was only enhanced following conditioning in the Lip CS+/tentacle CS− group but not in the Tentacle CS+/lip CS− group. The results show that the main features of differential appetitive classical conditioning can be recorded at the electrophysiological level, but some characteristics of the conditioned response are selectively expressed in the reduced preparation.
Two Cortical Areas Mediate Multisensory Integration in Superior Colliculus Neurons
Authors: Jiang Wan , Wallace Mark T. , Jiang Huai , Vaughan J. William , Stein Barry E.
Published: December 2017

The majority of multisensory neurons in the cat superior colliculus (SC) are able to synthesize cross-modal cues (e.g., visual and auditory) and thereby produce responses greater than those elicited by the most effective single modality stimulus and, sometimes, greater than those predicted by the arithmetic sum of their modality-specific responses. The present study examined the role of corticotectal inputs from two cortical areas, the anterior ectosylvian sulcus (AES) and the rostral aspect of the lateral suprasylvian sulcus (rLS), in producing these response enhancements. This was accomplished by evaluating the multisensory properties of individual SC neurons during reversible deactivation of these cortices individually and in combination using cryogenic deactivation techniques. Cortical deactivation eliminated the characteristic multisensory response enhancement of nearly all SC neurons but generally had little or no effect on a neuron's modality-specific responses. Thus, the responses of SC neurons to combinations of cross-modal stimuli were now no different from those evoked by one or the other of these stimuli individually. Of the two cortical areas, AES had a much greater impact on SC multisensory integrative processes, with nearly half the SC neurons sampled dependent on it alone. In contrast, only a small number of SC neurons depended solely on rLS. However, most SC neurons exhibited dual dependencies, and their multisensory enhancement was mediated by either synergistic or redundant influences from AES and rLS. Corticotectal synergy was evident when deactivating either cortical area compromised the multisensory enhancement of an SC neuron, whereas corticotectal redundancy was evident when deactivation of both cortical areas was required to produce this effect. The results suggest that, although multisensory SC neurons can be created as a consequence of a variety of converging tectopetal afferents that are derived from a host of subcortical and cortical structures, the ability to synthesize cross-modal inputs, and thereby produce an enhanced multisensory response, requires functional inputs from the AES, the rLS, or both.
The Parietal Reach Region Codes the Next Planned Movement in a Sequential Reach Task
Authors: Batista Aaron P. , Andersen Richard A.
Published: December 2017

Distinct subregions of the posterior parietal cortex contribute to planning different movements. The parietal reach region (PRR) is active during the delay period of a memory-guided reach task but generally not active during a memory-guided saccade task. We explored whether the reach planning activity in PRR is related to remembering targets for reaches or if it is related to specifying the reach that the monkey is about to perform. Monkeys were required to remember two target locations and then reach to them in sequence. Before the movements were executed, PRR neurons predominantly represented the reach about to be performed and only rarely represented the remembered target for the second reach. This indicates the area plays a role in specifying the target for the impending reach and may not contribute to storing the memory of subsequent reach targets.
Primate Horizontal Cell Dynamics: An Analysis of Sensitivity Regulation in the Outer Retina
Authors: Smith Vivianne C. , Pokorny Joel , Lee Barry B. , Dacey Dennis M.
Published: December 2017

The human cone visual system maintains sensitivity over a broad range of illumination, from below 1 troland to 1,000,000 trolands. While the cone photoreceptors themselves are an important locus for sensitivity regulation—or light adaptation—the degree to which they contribute in primates remains unclear. To determine the range of sensitivity regulation in the outer retina, the temporal dynamics, neural gain control, and response range compression were measured in second-order neurons, the H1 horizontal cells, of the macaque retina. Situated at the first synapse in the retina, H1 cells receive input from a large population of cones. Lee et al. have previously shown that sensitivity regulation in H1 cells is both cone type-specific and spatially restricted. The sensitivity regulation seen in H1 cells at moderate illuminances thus takes place before the summation of cone signals in these cells, and the data establish the H1 cell as a convenient locus for analyzing cone signals. In the present study, cone-driven responses of primate H1 cells to temporally modulated sine-wave stimuli and to increment pulses were measured at steady levels of 1–1,000 trolands. The H1 cell gave a modulated response to sine-wave stimuli and hyperpolarized to increment pulses with overshoots at stimulus onset and offset. The temporal amplitude sensitivity function was primarily low-pass in shape, with a small degree of low-frequency roll off and a resonance shoulder near 40 Hz. A model incorporating a cascade of first-order filters together with an underdamped second-order filter could describe both temporal sinusoidal and pulse hyperpolarizations. Amplitude sensitivity was estimated from both pulse and sine-wave data as a function of the steady adaptation level. Sensitivity at low light levels (1 troland) showed a slowing in temporal dynamics, indicating time-dependent sensitivity regulation. Sensitivity was reduced at light levels above approximately 10 trolands, reflecting both response range compression and neural gain control. Thus the outer retina is a major locus for sensitivity regulation in primates.
Muscle Synergies Encoded Within the Spinal Cord: Evidence From Focal Intraspinal NMDA Iontophoresis in the Frog
Authors: Saltiel Philippe , Wyler-Duda Kuno , D'Avella Andrea , Tresch Matthew C. , Bizzi Emilio
Published: December 2017

This paper relates to the problem of the existence of muscle synergies, that is whether the CNS command to muscles is simplified by controlling their activity in subgroups or synergies, rather than individually. We approach this problem with two methods that have been recently introduced: intraspinal N-methyl-d-aspartate (NMDA) microstimulation and a synergy-extracting algorithm. To search for a common set of synergies encoded for by the spinal cord whose combinations would account for a large range of electromyographic (EMG) patterns, we chose, rather than examining a large range of natural behaviors, to chemically microstimulate a large number of spinal cord interneuronal sites in different frogs. A possible advantage of this complementary method is that it is task-independent. Visual inspection suggested that the NMDA-elicited EMG patterns recorded from 12 leg muscles might indeed be constructed from smaller subgroups of muscles whose activity co-varied, suggestive of synergies. We used a modification of our extracting computational algorithm whereby a nonnegative least-squares method was employed to iteratively update both the synergies and their coefficients of activation in reconstructing the EMG patterns. Using this algorithm, a limited set of seven synergies was found whose linear combinations accounted for more than 91% of the variance in the pooled EMG data from 10 frogs, and more than 96% in individual frogs. The extracted synergies were similar among frogs. Further, preferred combinations of these synergies were clearly identified. This was found by extracting smaller sets of four, five, or six synergies and fitting each synergy from those sets as a combination from the set of seven synergies extracted from the same frog; the synergy combinations from each frog were then pooled together to examine their frequency of occurrence. Concordance with this method of identifying synergy combinations was found by examining how the synergies from the set of seven correlated pair-wise as they reconstructed the EMG data. These results support the existence of muscle synergies encoded within the spinal cord, which through preferred combinations, account for a large repertoire of spinal cord motor output. These findings are contrasted with previous approaches to the problem of synergies.
Axotomy- and Autotomy-Induced Changes in the Excitability of Rat Dorsal Root Ganglion Neurons
Authors: Abdulla Fuad A. , Smith Peter A.
Published: December 2017

The spontaneous, ectopic activity in sensory nerves that is induced by peripheral nerve injury is thought to contribute to the generation of “neuropathic” pain in humans. To examine the cellular mechanisms that underlie this activity, neurons in rat L4–L5 dorsal root ganglion (DRG) were first grouped as “large,” “medium,” or “small” on the basis of their size (input capacitance) and action potential (AP) shape. A fourth group of cells that exhibited a pronounced afterdepolarization (ADP) were defined as AD-cells. Whole cell recording was used to compare the properties of control neurons with those dissociated from rats in which the sciatic nerve had been sectioned (“axotomy” group) and with neurons from rats that exhibited self-mutilatory behavior in response to sciatic nerve section (“autotomy” group). Increases in excitability in all types of DRG neuron were seen within 2–7 wk of axotomy. Resting membrane potential (RMP) and the amplitude and duration of the afterhyperpolarization (AHP) that followed the AP were unaffected. Effects of axotomy were greatest in the small, putative nociceptive cells and least in the large cells. Moderate changes were seen in the medium and AD-cells. Compared to control neurons, axotomized neurons exhibited a higher frequency of evoked AP discharge in response to 500-ms depolarizing current injections; i.e., “gain” was increased and accommodation was decreased. The minimum current required to discharge an AP (rheobase) was reduced. There were significant increases in spike width in small cells and significant increases in spike height in small, medium, and AD-cells. The electrophysiological changes promoted by axotomy were intensified in animals that exhibited autotomy; spike height, and spike width were significantly greater than control for all cell types. Under our experimental conditions, spontaneous activity was never encountered in neurons dissociated from animals that exhibited autotomy. Thus changes in the electrical properties of cell bodies alone may not entirely account for injury-induced spontaneous activity in sensory nerves. The onset of autotomy coincided with alterations in the excitability of large, putative nonnociceptive, neurons. Thus large cells from the autotomy group were muchmore excitable than those from the axotomy group, whereas small cells from the autotomy group were only slightly more excitable. This is consistent with the hypothesis that the onset of autotomy is associated with changes in the properties of myelinated fibers. Changes in Ca2+ and K+ channel conductances that contribute to axotomy- and autotomy-induced changes in excitability are addressed in the accompanying paper.
Effect of Adrenalectomy on Membrane Properties and Synaptic Potentials in Rat Dentate Granule Cells
Authors: Joëls M. , Stienstra C. , Karten Y.
Published: December 2017

Adrenalectomy is known to accelerate both neurogenesis and cell death of granule cells located in the suprapyramidal blade of the rat dentate gyrus. Three days after adrenalectomy, some granule cells have already died by apoptosis while newly formed cells are not yet incorporated in the cell layer, resulting in a temporary loss of granule cells. Concomitantly, the field response to stimulation of perforant path afferents is reduced. While the temporary cell loss is likely to attenuate synaptic field responses, adrenalectomy-induced changes in properties of the surviving cells may also contribute to the reduction in field response amplitude. To address this possibility, we here investigated the membrane properties and synaptic responses of dentate granule cells, 3 days after adrenalectomy. We found that passive and most of the active membrane properties of granule cells in adrenalectomized rats were not significantly different from the cell properties in sham-operated controls. However, intracellularly recorded synaptic responses from surviving granule cells were markedly reduced after adrenalectomy. The N-methyl-d-aspartate (NMDA)– and the non-NMDA receptor–mediated components were reduced to a similar extent, suggesting that the attenuation of synaptic transmission after adrenalectomy could be partly of presynaptic origin. The data indicate that the earlier observed attenuation of synaptic field responses after adrenalectomy may be partly due to a diminished glutamatergic input to the dentate gyrus and not exclusively to a loss of granule cells participating in the synaptic circuit.
Whole Muscle Length-Tension Properties Vary With Recruitment and Rate Modulation in Areflexive Cat Soleus
Authors: Sandercock Thomas G. , Heckman C. J.
Published: December 2017

The length-tension relationship is a fundamental property of muscle. In its classic form, which is used in muscle models incorporated into studies of motor control, the length-tension relationship is measured during maximal activation via tetanic electrical stimulation in whole muscles or during high intracellular calcium levels in single muscle fibers. In this study, we measured the length-tension relationship of the cat soleus muscle during different levels of natural activation consisting of recruitment and rate modulation of motor units generated by the crossed extension reflex. The ipsilateral dorsal roots were cut to eliminate sensory feedback from the soleus. Length-tension was measured by large shortening steps that transiently allowed force to drop to zero. Force then recovered to a new steady value as the shorter length was maintained for several seconds. The effects of various levels of crossed extension activation on length-tension were compared with direct electrical stimulation of the muscle at 5, 10, 20, and 100 Hz. At all levels of crossed extension, the slope of the length-tension function was much steeper than the slope for tetanic stimulation at 100 Hz. Most slopes for crossed extension fell between the slopes seen with electrical stimulation at 10 and 20 Hz. There was a modest overall tendency for slope to decrease with the level of crossed extension activation. Because much of the normal movement repertoire requires submaximal activation, muscle models based on the tetanic length tension relationship will greatly underestimate the contribution of this relationship to force modulation at different muscle lengths.
Serine/Threonine Protein Phosphatases and Synaptic Inhibition Regulate the Expression of Cholinergic-Dependent Plateau Potentials
Authors: Fraser Douglas D. , Doll Daniel , MacVicar Brian A.
Published: December 2017

We previously identified cholinergic-dependent plateau potentials (PPs) in CA1 pyramidal neurons that were intrinsically generated by interplay between voltage-gated calcium entry and a Ca2+-activated nonselective cation conductance. In the present study, we examined both the second-messenger pathway and the role of synaptic inhibition in the expression of PPs. The stimulation of m1/m3 cholinergic receptor subtypes and G-proteins were critical for activating PPs because selective receptor antagonists (pirenzepine, hexahydro-sila-difenidol hydrochloride, 4-diphenylacetoxy- N-methylpiperidine methiodide) and intracellular guanosine-5′- O-(2-thiodiphosphate) prevented PP generation in carbachol. Intense synaptic stimulation occasionally activated PPs in the presence of oxytremorine M, a cholinergic agonist with preference for m1/m3 receptors. PPs were consistently activated by synaptic stimulation only when oxytremorine M was combined with antagonists at both GABAA and GABAB receptors. These latter data indicate an important role for synaptic inhibition in preventing PP generation. Both intrinsically generated and synaptically activated PPs could not be elicited following inhibition of serine/threonine protein phosphatases by calyculin A, okadaic acid, or microcystin-L, suggesting that muscarinic-induced dephosphorylation is necessary for PP generation. PP genesis was also inhibited following irreversible thiophosphorylation by intracellular perfusion with ATP-γ-S. These data indicate that the expression of cholinergic-dependent PPs requires protein phosphatase-induced dephosphorylation via G-protein–linked m1/m3 receptor(s). Moreover, synaptic inhibition via both GABAA and GABAB receptors normally prevents the synaptic activation of PPs. Understanding the regulation of PPs should provide clues to the role of this regenerative potential in both normal activity and pathophysiological processes such as epilepsy.
Unilateral Hearing Losses Alter Loud Sound-Induced Temporary Threshold Shifts and Efferent Effects in the Normal-Hearing Ear
Authors: Rajan R.
Published: December 2017

In animals with bilaterally normal hearing, olivocochlear pathways can protect the cochlea from the temporary shifts in hearing sensitivity (temporary threshold shifts; TTSs) caused by short-duration intense loud sounds. The crossed olivocochlear pathway provides protection during binaural loud sound, and uncrossed pathways protect when monaural or binaural loud sounds occur in noise backgrounds. Here I demonstrate that when there is a chronic unilateral hearing loss, effects of loud sounds, and efferent effects on loud sound, in the normal-hearing ear differ markedly from normal. Three categories of test animals with unilateral hearing loss were tested for effects at the normal-hearing ear. In all categories a monaural loud tone to the normal-hearing ear produced lower-than-normal TTSs, apparently because of a tonic re-setting of that ear's susceptibility to loud sound. Second, in the two test categories in which the hearing-loss ear was only partly damaged, binaural loud sound exacerbated TTSs in the normal-hearing ear because it caused threshold shifts that were a combination of “pure” TTSs and uncrossed efferent suppression of cochlear sensitivity. (In normal cats, this binaural tone results in crossed olivocochlear protection that reduces TTS.) Binaural loud sound did not produce such uncrossed efferent effects in the test category in which the nontest ear had suffered total hearing loss, suggesting that this uncrossed efferent effect required binaural input to the CNS. It is noteworthy that, in the absence of this uncrossed efferent suppression, the pure loud sound-alone induced TTSs after binaural exposure were low. Thus in the absence of any efferent effect, the normal-hearing cochlea had a reduced susceptibility to loud tone-induced damage. Finally, the results suggest that, with respect to cochlear actions at high sound levels, uncrossed and crossed efferent pathways may exert different effects at the one type of receptor cell.
Responses of Neurons in Neonatal Cortex and Thalamus to Patterned Visual Stimulation Through the Naturally Closed Lids
Authors: Krug Kristine , Akerman Colin J. , Thompson Ian D.
Published: December 2017

In studies of the developing mammalian visual system, it has been axiomatic that visual experience begins with eye-opening. Any role for neuronal activity earlier in development has been attributed to the patterned spontaneous activity found in retina and lateral geniculate nucleus (LGN). Here we show that, as early as 2 wk before eye-opening, visual stimuli presented through the closed eyelids can drive neuronal activity in LGN and striate cortex of the ferret. At this age, spontaneous activity in cortex is much lower than in LGN, and the visual responses of many cortical, but not geniculate, neurons depend on the orientation of a moving grating. Furthermore the selectivity of cortical neurons to the orientation of gratings presented through the closed eyelids improves with age. Thus neuronal activity patterned by visual experience, rather than by spontaneous retinal activity, is present in visual cortex much earlier than previously thought. This could have important implications for the self-organization of visual cortex.
Motor Control of Low-Threshold Motor Units in the Human Trapezius Muscle
Authors: Westgaard R. H. , De Luca C. J.
Published: December 2017

The firing pattern of low-threshold motor units was examined in the human trapezius and first dorsal interosseous (FDI) muscles during slowly augmenting, low-amplitude contractions that were intended to mimic contractile activity in postural muscles. The motor unit activity was detected with a special needle electrode and was analyzed with the assistance of computer algorithms. The surface electromyographic (EMG) signal was recorded. Its root-mean-square (RMS) value was calculated and presented to the subject who used it to regulate the muscle force level. In the trapezius, there was minimal, if any, firing rate modulation of early recruited motor units during slow contractions (≤1% EMGmax/s), and later recruited motor units consistently presented higher peak firing rates. As the force rate of the contraction increased (3% EMGmax/s), the firing rates of the motor units in the trapezius approached an orderly hierarchical pattern with the earliest recruited motor units having the greatest firing rate. In contrast, and as reported previously, the firing rates of all motor units in the FDI always presented the previously reported hierarchical “onion-skin” pattern. We conclude that the low-threshold motor units in the postural trapezius muscle, that is the motor units that are most often called on to activate the muscle in postural activities, have different control features in slow and fast contractions. More detailed analysis revealed that, in the low force-rate contractions of the trapezius, recruitment of new motor units inhibited the firing rate of active motor units, providing an explanation for the depressed firing rate of the low-threshold motor units. We speculate that Renshaw cell inhibition contributes to the observed deviation of the low-threshold motor units from the hierarchical onion-skin pattern.
Postnatal Development of Spike Generation in Rat Medial Vestibular Nucleus Neurons
Authors: Murphy Gabe J. , Du Lac Sascha
Published: December 2017

Image stability during self motion depends on the combined actions of the vestibuloocular and optokinetic reflexes (VOR and OKR, respectively). Neurons in the medial vestibular nucleus (MVN) participate in the VOR and OKR by firing in response to both head and image motion. Their intrinsic spike-generating properties enable MVN neurons to modulate firing rates linearly over a broad range of input amplitudes and frequencies such as those that occur during natural head and image motion. This study examines the postnatal development of the intrinsic spike-generating properties of rat MVN neurons with respect to maturation of peripheral vestibular and visual function. Spike generation was studied in a brain stem slice preparation by recording firing responses to current injected intracellularly through whole cell patch electrodes. MVN neurons fired spontaneously and modulated their firing rate in response to injected current at all postnatal ages. However, the input-output properties of the spike generator changed dramatically during the first two postnatal weeks. Neurons younger than postnatal day 10 could not fire faster than 80 spikes/s, modulated their firing rates over a limited range of input amplitudes, and tended to exhibit a nonlinear relationship between input current and mean evoked firing rate. In response to sustained depolarization, firing rates declined significantly in young neurons. Response gains tended to be highest in the first few postnatal days but varied widely across neurons and were not correlated with age. By about the beginning of the third postnatal week, MVN neurons could fire faster than 100 spikes/s in response to a broad range of input amplitudes, exhibited predominantly linear current-firing rate relationships, and adapted little in response to sustained depolarization. Concomitant decreases in action potential width and the time course of the afterhyperpolarization suggest that changes in potassium currents contribute to the maturation of the MVN neuronal spike generator. The results demonstrate that developmental changes in intrinsic membrane properties enable MVN neurons to fire linearly in response to a broad range of stimuli in time for the onset of visual function at the beginning of the third postnatal week.
Afterhyperpolarization Current in Myenteric Neurons of the Guinea Pig Duodenum
Authors: Vogalis Fivos , Furness John B. , Kunze Wolf A. A.
Published: December 2017

Whole cell patch and cell-attached recordings were obtained from neurons in intact ganglia of the myenteric plexus of the guinea pig duodenum. Two classes of neuron were identified electrophysiologically: phasically firing AH neurons that had a pronounced slow afterhyperpolarization (AHP) and tonically firing S neurons that lacked a slow AHP. We investigated the properties of the slow AHP and the underlying current ( I AHP) to address the roles of Ca2+ entry and Ca2+ release in the AHP and the characteristics of the K+channels that are activated. AH neurons had a resting potential of −54 mV and the AHP, which followed a volley of three suprathreshold depolarizing current pulses delivered at 50 Hz through the pipette, averaged 11 mV at its peak, which occurred 0.5–1 s following the stimulus. The duration of these AHPs averaged 7 s. Under voltage-clamp conditions, I AHP's were recorded at holding potentials of −50 to −65 mV, following brief depolarization of AH neurons (20–100 ms) to positive potentials (+35 to +50 mV). The null potential of the I AHP at its peak was −89 mV. The AHP and I AHP were largely blocked by ω-conotoxin GVIA (0.6–1 μM). Both events were markedly decreased by caffeine (2–5 mM) and by ryanodine (10–20 μM) added to the bathing solution. Pharmacological suppression of the I AHP with TEA (20 mM) or charybdotoxin (50–100 nM) unmasked an early transient inward current at −55 mV following step depolarization that reversed at −34 mV and was inhibited by niflumic acid (50–100 μM). Mean-variance analysis performed on the decay of the I AHPrevealed that the AHP K+ channels have a mean chord conductance of ∼10 pS, and there are ∼4,000 per AH neuron. Spectral analysis showed that the AHP channels have a mean open dwell time of 2.8 ms. Cell-attached patch recordings from AH neurons confirmed that the channels that open following action currents have a small unitary conductance (10–17 pS) and open with a high probability (≤0.5) within the first 2 s following an action potential. These results indicate that the AHP is largely a consequence of Ca2+ entry through ω-conotoxin GVIA-sensitive Ca2+ channels during the action potential, Ca2+-triggered Ca2+ release from caffeine-sensitive stores and the opening of Ca2+-sensitive small-conductance K+ channels.
Short-Term Plasticity at Inhibitory Synapses in Rat Striatum and Its Effects on Striatal Output
Authors: Fitzpatrick John S. , Akopian Garnik , Walsh John P.
Published: December 2017

Two forms of short-term plasticity at inhibitory synapses were investigated in adult rat striatal brain slices using intracellular recordings. Intrastriatal stimulation in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM) andd,l-2-amino-5-phosphonovaleric acid (50 μM) produced an inhibitory postsynaptic potential (IPSP) that reversed polarity at −76 ± 1 (SE) mV and was sensitive to bicuculline (30 μM). The IPSP rectified at hyperpolarized membrane potentials due in part to activation of K+ channels. The IPSP exhibited two forms of short-term plasticity, paired-pulse depression (PPD) and synaptic augmentation. PPD lasted for several seconds and was greatest at interstimulus intervals (ISIs) of several hundred milliseconds, reducing the IPSP to 80 ± 2% of its control amplitude at an ISI of 200 ms. Augmentation of the IPSP, elicited by a conditioning train of 15 stimuli applied at 20 Hz, was 119 ± 1% of control when sampled 2 s after the conditioning train. Augmentation decayed with a time constant of 10 s. We tested if PPD and augmentation modify the ability of the IPSP to prevent the generation of action potentials. A train of action potentials triggered by a depolarizing current injection of constant amplitude could be interrupted by stimulation of an IPSP. If this IPSP was the second in a pair of IPSPs, it was less effective in blocking spikes due to PPD. By contrast, augmented IPSPs were more effective in blocking spikes. The same results were achieved when action potentials were triggered by a depolarizing current injection of varying amplitude, a manipulation that produces nearly identical spike times from trial to trial and approximates the in vivo behavior of these neurons. These results demonstrate that short-term plasticity of inhibition can modify the output of the striatum and thus may be an important component of information processing during behaviors that involve the striatum.
Postnatal Development of Inhibitory Synaptic Transmission in the Rostral Nucleus of the Solitary Tract
Authors: Grabauskas Gintautas , Bradley Robert M.
Published: December 2017

To explore the postnatal development of inhibitory synaptic activity in the rostral (gustatory) nucleus of the solitary tract (rNST), whole cell and gramicidin perforated patch-clamp recordings were made in five age groups of rats [ postnatal day 0–7 ( P0–7), P8–14, P15–21, P22–30, and P > 55]. The passive membrane properties of the developing rNST neurons as well as the electrophysiological and pharmacological characteristics of single and tetanic stimulus-evoked inhibitory postsynaptic potentials (IPSPs) were studied in brain slices under glutamate receptor blockade. During the first postnatal weeks, significant changes in resting membrane potential, spontaneous activity, input resistance, and neuron membrane time constant of the rNST neurons occurred. Although all the IPSPs recorded were hyperpolarizing, the rise and decay time constants of the single stimulus shock-evoked IPSPs decreased, and the inhibition response–concentration function to the γ-aminobutyric acid (GABA) receptor antagonist bicuculline methiodide (BMI) shifted to the left during development. In P0–7 and P8–14, but not in older animals, the IPSPs had a BMI-insensitive component that was sensitive to block by picrotoxin, suggesting a transient expression of GABAC receptors. Tetanic stimulation resulted in both short- and long-term changes of inhibitory synaptic transmission in the rNST. For P0–7 and P8–14 animals tetanic stimulation resulted in a sustained hyperpolarization that was maintained for some time after termination of the tetanic stimulation. In contrast, tetanic stimulation of neurons in P15–21 and older animals resulted in hyperpolarization that was not sustained but decayed back to a more positive level with an exponential time course. Tetanic stimulation resulted in potentiation of single stimulus shock-evoked IPSPs in ∼50% of neurons in all age groups. These developmental changes in inhibitory synaptic transmission in the rNST may play an important role in shaping synaptic activity in early development of the rat gustatory system during a time of maturation of taste preferences and aversions.
Effects of Characteristic Dendritic Tip Geometry on the Electrical Properties of Teleost Thalamic Neurons
Authors: Tsutsui Hidekazu , Oka Yoshitaka
Published: December 2017

Of the factors that characterize the properties and functions of neurons, dendritic geometry is one of the most critical. We used simulations employing the multi-compartment model to study the effects of dendritic tip geometry on the electrical properties of the “large cell” in a teleost thalamic nucleus from the corpus glomerulosum. We demonstrated a dramatic geometrical “boosting” effect; passive propagation of the synaptic inputs from the dendritic tip to the soma through the dendritic stalk is less attenuated in cells with larger tips.
Throwing Accuracy in the Vertical Direction During Prism Adaptation: Not Simply Timing of Ball Release
Authors: Martin Tod A. , Greger Bradley E. , Norris Scott A. , Thach W. Thomas
Published: December 2017

In a previous study, others have hypothesized that the variance in vertical errors that occurs while throwing at visual targets is caused by changes in any of three throw parameters: hand location in space, hand translational velocity, and hand orientation. From an analysis of skilled throwers, those authors concluded that vertical error is best correlated with variance in hand orientation, which in turn is related to the timing of ball release. We used a vertical prism adaptation paradigm to investigate which of these throwing parameters subjects use when adapting to external perturbation. Our subjects showed no correlation between hand position or hand translational velocity and ball impact height in normal, over-practiced throwing. However, video-based motion analysis showed that modifications both of position and speed of the hand play an important role when subjects are forced to compensate for a vertically shifting prism perturbation during a dart-like throw (these factors contribute ∼30% of the adaptation). We concluded that, during adaptation, more degrees of freedom and more sources of potential error are modified to achieve the gaze–throw recalibration required to hit the target than are employed in this type of throw during normal conditions.
Three-Dimensional Binocular Kinematics of Torsional Vestibular Nystagmus During Convergence on Head-Fixed Targets in Humans
Authors: Bergamin O. , Straumann D.
Published: December 2017

When a human subject is oscillated about the nasooccipital axis and fixes upon targets along the horizontal head-fixed meridian, angular eye velocity includes a vertical component that increases with the horizontal eccentricity of the line-of-sight. This vertical eye movement component is necessary to prevent retinal slip. We asked whether fixation on a near head-fixed target during the same torsional vestibular stimulation would lead to differences of vertical eye movements between the right and the left eye, as the directions of the two lines-of-sight are not parallel during convergence. Healthy human subjects ( n = 6) were oscillated (0.3 Hz, ±30°) about the nasooccipital axis on a three-dimensional motor-driven turntable. Binocular movements were recorded using the dual search coil technique. A head-fixed laser dot was presented 1.4 m (far head-fixed target) or 0.25 m (near head-fixed target) in front of the right eye. We found highly significant ( P < 0.01) correlations (R binocular = 0.8, monocular = 0.59) between the convergence angle and the difference of the vertical eye velocity between the two eyes. The slope of the fitted linear regression between the two parameters ( s = 0.45) was close to the theoretical slope necessary to prevent vertical retinal slippage (predicted s = 0.5). Covering the left eye did not significantly change the slope ( s = 0.52). In addition, there was a marked gain reduction (∼35%) of the torsional vestibuloocular reflex (VOR) between viewing the far and the near targets, confirming earlier results by others. There was no difference in torsional gain reduction between the two eyes. Lenses of +3 dpt positioned in front of both eyes to decrease the amount of accommodation did not further change the gain of the torsional VOR. In conclusion, ocular convergence on a near head-fixed target during torsional vestibular stimulation leads to deviations in vertical angular velocity between the two eyes necessary to prevent vertical double vision. The vertical deviation velocity is mainly linked to the amount of convergence, since it also occurs during monocular viewing of the near head-fixed target. This suggests that convergence during vestibular stimulation automatically leads to an alignment of binocular rotation axes with the visual axes independent of retinal slip.