bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Spontaneous Synaptic Activity of Amacrine Cells in the Mouse Retina
Authors: Frech Moritz J. , Pérez-León Jorge , Wässle Heinz , Backus Kurt H.
Published: December 2017

Amacrine cells are a heterogeneous class of interneurons that modulate the transfer of the light signals through the retina. In addition to ionotropic glutamate receptors, amacrine cells express two types of inhibitory receptors, GABAA receptors (GABAARs) and glycine receptors (GlyRs). To characterize the functional contribution of these different receptors, spontaneous postsynaptic currents (sPSCs) were recorded with the whole cell configuration of the patch-clamp technique in acutely isolated slices of the adult mouse retina. All amacrine cells investigated ( n = 47) showed spontaneous synaptic activity. In six amacrine cells, spontaneous excitatory postsynaptic currents could be identified by their sensitivity to kynurenic acid. They were characterized by small amplitudes [mean: −13.7 ± 1.5 (SE) pA] and rapid decay kinetics (mean τ: 1.35 ± 0.16 ms). In contrast, the reversal potential of sPSCs characterized by slow decay kinetics (amplitude-weighted time constant, τw, >4 ms) was dependent on the intracellular Cl− concentration ( n = 7), indicating that they were spontaneous inhibitory postsynaptic currents (sIPSCs). In 14 of 34 amacrine cells sIPSCs were blocked by bicuculline (10 μM), indicating that they were mediated by GABAARs. Only four amacrine cells showed glycinergic sIPSCs that were inhibited by strychnine (1 μM). In one amacrine cell, sIPSCs mediated by GABAARs and GlyRs were found simultaneously. GABAergic sIPSCs could be subdivided into one group best fit by a monoexponential decay function and another biexponentially decaying group. The mean amplitude of GABAergic sIPSCs (−42.1 ± 5.8 pA) was not significantly different from that of glycinergic sIPSCs (−28.0 ± 8.5 pA). However, GlyRs (mean T10/90: 2.4 ± 0.08 ms) activated significantly slower than GABAARs (mean T10/90: 1.2 ± 0.03 ms). In addition, the decay kinetics of monoexponentially decaying GABAARs (mean τw: 20.3 ± 0.50), biexponentially decaying GABAARs (mean τw: 30.7 ± 0.95), and GlyRs (mean τw = 25.3 ± 1.94) were significantly different. These differences in the activation and decay kinetics of sIPSCs indicate that amacrine cells of the mouse retina express at least three types of functionally different inhibitory receptors: GlyRs and possibly two subtypes of GABAARs.
NR2B-Containing NMDA Autoreceptors at Synapses on Entorhinal Cortical Neurons
Authors: Woodhall Gavin , Evans D. Ieuan , Cunningham Mark O. , Jones Roland S. G.
Published: December 2017

We have previously shown that presynaptic N-methyl-d-aspartate receptors (NMDARs) can facilitate glutamate release onto principal neurons in the entorhinal cortex (EC). In the present study, we have investigated the subunit composition of these presynaptic NMDARs. We recorded miniature α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor–mediated excitatory postsynaptic currents (mEPSCs), from visually identified neurons in layers II and V of the EC in vitro. In both layers, bath application of the NR2A/B subunit–selective agonist, homoquinolinic acid (HQA), resulted in a marked facilitation of mEPSC frequency. Blockade of presynaptic Ca2+entry through either NMDARs or voltage-gated Ca2+channels with Co2+prevented the effects of HQA, confirming that Ca2+entry to the terminal was required for facilitation. When the NR2B-selective antagonist, ifenprodil, was applied prior to HQA, the increase in mEPSC frequency was greatly reduced. In addition, we found that an NMDAR antagonist blocked frequency-dependent facilitation of evoked release and reduced mEPSC frequency in layer V. Thus we have demonstrated that NMDA autoreceptors in layer V of the EC bear the NR2B subunit, and that NMDARs are also present at terminals onto superficial neurons.
Zinc and Copper Influence Excitability of Rat Olfactory Bulb Neurons by Multiple Mechanisms
Authors: Horning Michelle S. , Trombley Paul Q.
Published: December 2017

Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiological recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and voltage-gated ion channels. Application of either zinc or copper eliminated GABA-mediated spontaneous inhibitory postsynaptic potentials. However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc. Among voltage-gated ion channels, zinc or copper inhibited TTX-sensitive sodium channels and delayed rectifier-type potassium channels but did not prevent the firing of evoked single action potentials or dramatically alter their kinetics. Zinc and copper had distinct effects on transient A-type potassium currents. Whereas copper only inhibited the A-type current, zinc modulation of A-type currents resulted in either potentiation or inhibition of the current depending on the membrane potential. The effects of zinc and copper on potassium channels likely underlie their effects on repetitive firing in response to long-duration step depolarizations. Copper reduced repetitive firing independent of the initial membrane voltage. In contrast, whereas zinc reduced repetitive firing at membrane potentials associated with zinc-mediated enhancement of the A-type current (−50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inhibition of the A-type current (−90 mV). Application of zinc or copper also inhibited voltage-gated Ca2+ channels, suggesting a possible role for presynaptic modulation of neurotransmitter release. Despite similarities between the effects of zinc and copper on some ligand- and voltage-gated ion channels, these data suggest that their net effects likely contribute to differential modulation of neuronal excitability.
Functional Overlap of Finger Representations in Human SI and SII Cortices
Authors: Simões Cristina , Mertens Markus , Forss Nina , Jousmäki Veikko , Lütkenhöner Bernd , Hari Riitta
Published: December 2017

We aimed to find out to what extent functional representations of different fingers of the two hands overlap at the human primary and secondary somatosensory cortices SI and SII. Somatosensory evoked fields (SEFs) were recorded with a 306-channel neuromagnetometer from 8 subjects. Tactile stimuli, produced by diaphragms driven by compressed air, were delivered to the fingertips in three different conditions. First, the right index finger was stimulated once every 2 s. Then two other stimuli were interspersed, in different sessions, to right- or left-hand fingers (thumb, middle finger, or ring finger) between the successive right index finger stimuli. Strengths of the responses to right index finger stimuli were evaluated in each condition. Responses to right index finger stimuli were modeled by three current dipoles, located at the contralateral SI and the SII cortices of both hemispheres. The earliest SI responses, peaking around 65 ms, were suppressed by 18% ( P < 0.05) when the intervening stimuli were presented to the same hand; intervening stimuli to the other hand had no effect. The SII responses were bilaterally suppressed by intervening stimuli presented to either hand: in the left SII, the suppression was 39 and 42% ( P < 0.01) and in the right SII 67 and 72% ( P < 0.001) during left- and right-sided intervening stimuli, respectively. Left- and right-sided intervening stimuli affected similarly the SII responses and had no effect on the response latencies. The results indicate a strong and symmetric overlap of finger representations for both hands in the human SII cortices, and a weaker functional overlap for fingers of the same hand in the SI cortex.
Neck Muscles in the Rhesus Monkey. I. Muscle Morphometry and Histochemistry
Authors: Richmond Frances J. R. , Singh Kan , Corneil Brian D.
Published: December 2017

Morphometric methods were used to describe the musculotendinous lengths, fascicle lengths, pennation angles, and cross-sectional areas of neck muscles in adult Macaca mulatta monkeys. Additionally, muscles were frozen, sectioned, and stained for ATPase activity to determine fiber-type composition. Individual rhesus muscles were found to vary widely in their degree of similarity to feline and human muscles studied previously. Suboccipital muscles and muscles supplied by the spinal accessory nerve were most similar to human homologs, whereas most other muscles exhibited architectural specializations. Many neck muscles were architecturally complex, with multiple attachments and internal aponeuroses or tendinous inscriptions that affected the determination of their cross-sectional areas. All muscles were composed of a mixture of type I, IIa, and IIb fiber types the relative proportions of which varied. Typically, head-turning muscles had lower proportions of type II (fast) fibers than homologous feline muscles, whereas extensor muscles contained higher proportions of type II fibers. The physical and histochemical specializations described here are known to have a direct bearing on functional properties, such as force-developing capacity and fatigue-resistance. These specializations must be recognized if muscles are to be modeled accurately or studied electrophysiologically.
Neck Muscles in the Rhesus Monkey. II. Electromyographic Patterns of Activation Underlying Postures and Movements
Authors: Corneil Brian D. , Olivier Etienne , Richmond Frances J. R. , Loeb Gerald E. , Munoz Douglas P.
Published: December 2017

Electromyographic (EMG) activity was recorded in ≤12 neck muscles in four alert monkeys whose heads were unrestrained to describe the spatial and temporal patterns of neck muscle activation accompanying a large range of head postures and movements. Some head postures and movements were elicited by training animals to generate gaze shifts to visual targets. Other spontaneous head movements were made during orienting, tracking, feeding, expressive, and head-shaking behaviors. These latter movements exhibited a wider range of kinematic patterns. Stable postures and small head movements of only a few degrees were associated with activation of a small number of muscles in a reproducible synergy. Additional muscles were recruited for more eccentric postures and larger movements. For head movements during trained gaze shifts, movement amplitude, velocity, and acceleration were correlated linearly and agonist muscles were recruited without antagonist muscles. Complex sequences of reciprocal bursts in agonist and antagonist muscles were observed during very brisk movements. Turning movements of similar amplitudes that began from different initial head positions were associated with systematic variations in the activities of different muscles and in the relative timings of these activities. Unique recruitment synergies were observed during feeding and head-shaking behaviors. Our results emphasize that the recruitment of a given muscle was generally ordered and consistent but that strategies for coordination among various neck muscles were often complex and appeared to depend on the specifics of musculoskeletal architecture, posture, and movement kinematics that differ substantially among species.
Excitatory Postsynaptic Potentials Trigger a Plateau Potential in Rat Subthalamic Neurons at Hyperpolarized States
Authors: Otsuka Takeshi , Murakami Fujio , Song Wen-Jie
Published: December 2017

The subthalamic nucleus (STN) directly innervates the output structures of the basal ganglia, playing a key role in basal ganglia function. It is therefore important to understand the regulatory mechanisms for the activity of STN neurons. In the present study, we aimed to investigate how the intrinsic membrane properties of STN neurons interact with their synaptic inputs, focusing on their generation and the properties of the long-lasting, plateau potential. Whole cell recordings were obtained from STN neurons in slices prepared from postnatal day 14 (P14) to P20 rats. We found that activation of glutamate receptor-mediated excitatory synaptic potentials (EPSPs) evoked a plateau potential in a subpopulation of STN neurons ( n = 13/22), in a voltage-dependent manner. Plateau potentials could be induced only when the cell was hyperpolarized to more negative than about −75 mV. Plateau potentials, evoked with a depolarizing current pulse, again only from a hyperpolarized state, were observed in about half of STN neurons tested ( n = 162/327). Only in neurons in which a plateau potential could be evoked by current injection did EPSPs evoke plateau potentials. L-type Ca2+ channels, Ca2+-dependent K+ channels, and TEA-sensitive K+ channels were found to be involved in the generation of the potential. The stability of the plateau potential, tested by the injection of a negative pulse current during the plateau phase, was found to be robust at the early phase of the potential, but decreased toward the end. As a result the early part of the plateau potential was resistant to membrane potential perturbations and would be able to support a train of action potentials. We conclude that excitatory postsynaptic potentials, evoked in a subpopulation of STN neurons at a hyperpolarized state, activate L-type Ca2+ and other channels, leading to the generation of a plateau potential. Thus about half of STN neurons can transform short-lasting synaptic excitation into a long train of output spikes by voltage-dependent generation of a plateau potential.
Indirectly Gated Cl−-Dependent Cl−Channels Sense Physiological Changes of Extracellular Chloride in the Leech
Authors: Wenning Angela , Erxleben Christian F. J. , Calabrese Ronald L.
Published: December 2017

The maintenance of ion homeostasis requires adequate ion sensors. In leeches, 34 nephridial nerve cells (NNCs) monitor the Cl−concentration of the blood. After a blood meal, the Cl−concentration of leech blood triples and is gradually restored to its normal value within 48 h after feeding. As previously shown in voltage-clamp experiments, the Cl−sensitivity of the NNCs relies on a persistent depolarizing Cl−current that is turned off by an increase of the extracellular Cl−concentration. The activation of this Cl−-dependent Cl−current is independent of voltage and of extra- and intracellular Ca2+. The transduction mechanism is now characterized on the single-channel level. The NNC's sensitivity to Cl−is mediated by a slowly gating Cl−-dependent Cl−channel with a mean conductance of 50 pS in the cell-attached configuration. Gating of the Cl−channel is independent of voltage, and channel activity is independent of extra- and intracellular Ca2+. Channel activity and the macroscopic current are reversibly blocked by bumetanide. In outside-out patches, changes of the extracellular Cl−concentration do not affect channel activity, indicating that channel gating is not via direct interaction of extracellular Cl−with the channel. As shown by recordings in the cell-attached configuration, the activity of the channels under the patch is instead governed by the Cl−concentration sensed by the rest of the cell. We postulate a membrane-bound Cl−-sensing receptor, which—on the increase of the extracellular Cl−concentration—closes the Cl−channel via a yet unidentified signaling pathway.
Plateau Potentials in Sacrocaudal Motoneurons of Chronic Spinal Rats, Recorded In Vitro
Authors: Bennett David J. , Li Yunru , Siu Merek
Published: December 2017

Intracellular recordings were made from sacrocaudal tail motoneurons of acute and chronic spinal rats to examine whether plateau potentials contribute to spasticity associated with chronic injury. The spinal cord was transected at the S2 level, causing, over time, exaggerated long-lasting reflexes (hyperreflexia) associated with a general spasticity syndrome in the tail muscles of chronic spinal rats (1–5 mo postinjury). The whole sacrocaudal spinal cord of chronic or acute spinal rats was removed and maintained in vitro in normal artificial cerebral spinal fluid (ACSF). Hyperreflexia in chronic spinal rats was verified by recording the long-lasting ventral root responses to dorsal root stimulation in vitro. The intrinsic properties of sacrocaudal motoneurons were studied using intracellular injections of slow triangular current ramps or graded current pulses. In chronic spinal rats, the current injection triggered sustained firing and an associated sustained depolarization ( plateau potential; 34/35 cells; mean, 5.5 mV; duration >5 s; normal ACSF). The threshold for plateau initiation was low and usually corresponded to an acceleration in the membrane potential just before recruitment. After recruitment and plateau activation, the firing rate changed linearly with current during the slow ramps [63% of cells had a linear frequency-current ( F-I) relation] despite the presence of the plateau. The persistent inward current ( I PIC) producing the plateau and sustained firing was estimated to be on average 0.8 nA as determined by the reduction in injected current needed to stop the sustained firing [Δ I = −0.8 ± 0.6 (SD) nA], compared with the current needed to start firing ( I = 1.7 ± 1.5 nA; 47% reduction). In motoneurons of acute spinal rats, plateaus were rarely seen (3/22), although they could be made to occur with bath application of serotonin. In motoneurons of chronic spinal rats there were no significant changes in the mean passive input resistance, rheobase or amplitude of the spike afterhyperpolarization (AHP) as compared with acute spinal rats. However, there were significant increases in AHP duration and initial firing rate at recruitment and decreases in minimum firing rate and F-I slope. We suggest that the higher initial firing rate resulted from the plateau activation at recruitment and the lower F-I slope resulted from an increase in active conductance during firing, due to I PIC. Brief dorsal root stimulation also triggered a plateau and sustained discharge (long-lasting reflexes; 2–5 s) in motoneurons of chronic (but not acute) spinal rats. When the plateau was eliminated by a hyperpolarizing current bias, the reflex response was significantly shortened (to 1 s). Thus plateaus contributed substantially to the long-lasting reflexes in vitro and therefore should contribute significantly to the corresponding exaggerated reflexes and spasticity in awake chronic spinal rats.
Neural Correlates for Roughness Choice in Monkey Second Somatosensory Cortex (SII)
Authors: Pruett J. R. , Sinclair R. J. , Burton H.
Published: December 2017

This experiment explored the relationship between neural firing patterns in second somatosensory cortex (SII) and decisions about roughness of tactile gratings. Neural and behavioral data were acquired while monkeys made dichotomous roughness classifications of pairs of gratings that differed in groove width (1.07 vs. 1.90 and 1.42 vs. 2.53 mm). A computer-controlled device delivered the gratings to a single immobilized finger pad. In one set of experiments, three levels of contact force (30, 60, and 90 g) were assigned to these gratings at random. In another set of experiments, three levels of scanning speed (40, 80, and 120 mm/s) were assigned to these gratings at random. Groove width was the intended variable for roughness. Force variation disrupted the monkeys' groove-width (roughness) classifications more than did speed variation. A sample of 32 SII cells showed correlated changes in firing (positive or negative effects of both variables) when groove width and force increased. While these cells were recorded, the monkeys made roughness classification errors, confusing wide groove-width gratings at low force with narrow groove-width gratings at high force. Three-dimensional plots show how some combinations of groove width and force perturbed the monkeys' trial-wise classifications of grating roughness. Psychometric functions show that errors occurred when firing rates failed to distinguish gratings. A possible interpretation is that when asked to classify grating roughness, the monkeys based classifications on the firing rates of a subset of roughness-sensitive cells in SII. Results support human psychophysical data and extend the roughness range of a model of the effects of groove width and force on roughness. One monkey's SII neural sample (21 cells) showed significant correlation between firing rate response functions for groove width and speed (both correlations either positive or negative). Only that monkey showed a statistically significant interaction between groove width and speed on roughness classification performance. This additional finding adds weight to the argument that SII cell firing rates influenced monkey roughness classifications.
Asymmetric Propagation of Spreading Depression Along the Anteroposterior Axis of the Cerebral Cortex in Mice
Authors: Godukhin Oleg V. , Obrenovitch Tihomir P.
Published: December 2017

The purpose of this study was to ascertain whether or not spreading depression (CSD) propagates symmetrically along the anteroposterior axis of the cortex of mice, and to determine where CSD should be elicited to achieve a uniform exposure of the cortex to this phenomenon. Experiments were performed in halothane-anesthetized mice, with three different locations aligned 1.5 mm from the midline used for either KCl elicitation of CSD or the recording of its propagation. Our results demonstrated that, at least in the mouse cortex, CSD propagated much more effectively from posterior to anterior regions than in the opposite direction. This feature was due to a different efficacy of propagation in the two opposite directions, and not to a reduced susceptibility of occipital regions to CSD elicitation. Heterogeneous CSD propagation constitutes a potential pitfall for neurochemical studies of post-CSD changes in mice, as brain tissue samples collected for this purpose should be uniformly exposed to CSD. Occipital sites for CSD induction are clearly optimal for this purpose. If CSD propagation is confirmed to be more effective from posterior to anterior regions in other species, this may be relevant to the pathophysiology of classical migraine because the most frequent aura symptoms (i.e., visual disturbances) originate in the occipital cortex.
Neural Readaptation to Earth's Gravity Following Return From Space
Authors: Boyle Richard , Mensinger Allen F. , Yoshida Kaoru , Usui Shiro , Intravaia Anthony , Tricas Timothy , Highstein Stephen M.
Published: December 2017

The consequence of exposure to microgravity on the otolith organs was studied by recording the responses of vestibular nerve afferents supplying the utricular otolith organ to inertial accelerations in four toadfish, Opsanus tau, sequentially for 5 days following two National Aeronautics and Space Administration shuttle orbital flights. Within the first day postflight, the magnitude of response to an applied translation was on average three times greater than for controls. The reduced gravitational acceleration in orbit apparently resulted in an upregulation of the sensitivity of utricular afferents. By 30 h postflight, responses were statistically similar to control. The time course of return to normal afferent sensitivity parallels the reported decrease in vestibular disorientation in astronauts following return from space.
Constraints on Somatotopic Organization in the Primary Motor Cortex
Authors: Schieber Marc H.
Published: December 2017

Since the 1870s, the primary motor cortex (M1) has been known to have a somatotopic organization, with different regions of cortex participating in control of face, arm, and leg movements. Through the middle of the 20th century, it seemed possible that the principle of somatotopic organization extended to the detailed representation of different body parts within each of the three major representations. The arm region of M1, for example, was thought to contain a well-ordered, point-to-point representation of the movements or muscles of the thumb, index, middle, ring, and little fingers, the wrist, elbow, and shoulder, as conveyed by the iconic homunculus and simiusculus. In the last quarter of the 20th century, however, experimental evidence has accumulated indicating that within-limb somatotopy in M1 is not spatially discrete nor sequentially ordered. Rather, beneath gradual somatotopic gradients of representation, the representations of different smaller body parts or muscles each are distributed widely within the face, arm, or leg representation, such that the representations of any two smaller parts overlap extensively. Appreciation of this underlying organization will be essential to further understanding of the contribution to control of movement made by M1. Because no single experiment disproves a well-ordered within-limb somatotopic organization in M1, here I review the accumulated evidence, using a framework of six major features that constrain the somatotopic organization of M1: convergence of output, divergence of output, horizontal interconnections, distributed activation, effects of lesions, and ability to reorganize. Review of the classic experiments that led to development of the homunculus and simiusculus shows that these data too were consistent with distributed within-limb somatotopy. I conclude with speculations on what the constrained somatotopy of M1 might tell us about its contribution to control of movement.
Relationship Between Simulated Common Synaptic Input and Discharge Synchrony in Cat Spinal Motoneurons
Authors: Binder Marc D. , Powers Randall K.
Published: December 2017

Synchronized discharge of individual motor units is commonly observed in the muscles of human subjects performing voluntary contractions. The amount of this synchronization is thought to reflect the extent to which motoneurons in the same and related pools share common synaptic input. However, the relationship between the proportion of shared synaptic input and the strength of synchronization has never been measured directly. In this study, we simulated common shared synaptic input to cat spinal motoneurons by driving their discharge with noisy, injected current waveforms. Each motoneuron was stimulated with a number of different injected current waveforms, and a given pair of waveforms were either completely different or else shared a variable percentage of common elements. Cross-correlation histograms were then compiled between the discharge of motoneurons stimulated with noise waveforms with variable degrees of similarity. The strength of synchronization increased with the amount of simulated “common” input in a nonlinear fashion. Moreover, even when motoneurons had >90% of their simulated synaptic inputs in common, only ∼25–45% of their spikes were synchronized. We used a simple neuron model to explore how variations in neuron properties during repetitive discharge may lead to the low levels of synchronization we observed experimentally. We found that small variations in spike threshold and firing rate during repetitive discharge lead to large decreases in synchrony, particularly when neurons have a high degree of common input. Our results may aid in the interpretation of studies of motor unit synchrony in human hand muscles during voluntary contractions.
Afferent Fibers of the Hypogastric Nerves Are Involved in the Facilitating Effects of Chemical Bladder Irritation in Rats
Authors: Mitsui Takahiko , Kakizaki Hidehiro , Matsuura Shinobu , Ameda Kaname , Yoshioka Mitsuhiro , Koyanagi Tomohiko
Published: December 2017

To evaluate the role of bladder afferent fibers in the hypogastric nerves (HGN) in modulation of the micturition reflex induced by chemical bladder irritation, voiding behavior, continuous cystometry, and spinal c-fos expression following intravesical acetic acid instillation were investigated in rats with or without HGN transection. Voiding behavior and continuous cystometry were examined in unanesthetized conscious rats. Following chemical bladder irritation, a significant increase in urinary frequency associated with a marked decrease in the voided volume per micturition, was noted in control rats with the intact HGN, but not in HGN-transected rats. Continuous infusion of acetic acid in control rats elicited irritative bladder responses characterized by a marked decrease in the intercontraction interval and a marked increase in maximal vesical pressure, both of which were absent in capsaicin-desensitized rats. HGN transection prevented the decrease in the intercontraction interval but not an increase in maximal vesical pressure following chemical bladder irritation. Compared with saline infusion, acetic acid infusion caused a significant increase in c-fos expression at L1 and L6 of the spinal cord, and HGN transection significantly reduced c-fos expression in the dorsal horn of the spinal cord at L1 but not at L6. These results suggest that capsaicin-sensitive bladder afferent fibers in the HGN, which travel through the rostral lumbar spinal cord, have a role in urinary frequency caused by chemical bladder irritation.
Potassium Currents in Octopus Cells of the Mammalian Cochlear Nucleus
Authors: Bal Ramazan , Oertel Donata
Published: December 2017

Octopus cells in the posteroventral cochlear nucleus (PVCN) of mammals are biophysically specialized to detect coincident firing in the population of auditory nerve fibers that provide their synaptic input and to convey its occurrence with temporal precision. The precision in the timing of action potentials depends on the low input resistance (∼6 MΩ) of octopus cells at the resting potential that makes voltage changes rapid (τ ∼ 200 μs). It is the activation of voltage-dependent conductances that endows octopus cells with low input resistances and prevents repetitive firing in response to depolarization. These conductances have been examined under whole cell voltage clamp. The present study reveals the properties of two conductances that mediate currents whose reversal at or near the equilibrium potential for K+ over a wide range of extracellular K+ concentrations identifies them as K+ currents. One rapidly inactivating conductance, g KL, had a threshold of activation at −70 mV, rose steeply as a function of depolarization with half-maximal activation at −45 ± 6 mV (mean ± SD), and was fully activated at 0 mV. The low-threshold K+ current ( I KL) was largely blocked by α-dendrotoxin (α-DTX) and partially blocked by DTX-K and tityustoxin, indicating that this current was mediated through potassium channels of the Kv1 (also known as shakeror KCNA) family. The maximum low-threshold K+conductance ( g KL) was large, 514 ± 135 nS. Blocking I KL with α-DTX revealed a second K+ current with a higher threshold ( I KH) that was largely blocked by 20 mM tetraethylammonium (TEA). The more slowly inactivating conductance, g KH, had a threshold for activation at −40 mV, reached half-maximal activation at −16 ± 5 mV, and was fully activated at +30 mV. The maximum high-threshold conductance, g KH, was on average 116 ± 27 nS. The present experiments show that it is not the biophysical and pharmacological properties but the magnitude of the K+ conductances that make octopus cells unusual. At the resting potential, −62 mV, g KLcontributes ∼42 nS to the resting conductance and mediates a resting K+ current of 1 nA. The resting outward K+ current is balanced by an inward current through the hyperpolarization-activated conductance, g h, that has been described previously.
Response Adaptation of Medial Olivocochlear Neurons Is Minimal
Authors: Brown M. C.
Published: December 2017

Response adaptation is a general characteristic of neurons. A number of studies have investigated the adaptation characteristics of auditory-nerve fibers, which send information to the brain about sound stimuli. However, there have been no previous adaptation studies of olivocochlear neurons, which provide efferent fibers to hair cells and auditory nerve dendrites in the auditory periphery. To study adaptation in efferent fibers, responses of single olivocochlear neurons were recorded to characteristic-frequency tones and noise, using anesthetized guinea pigs. To measure short-term adaptation, stimuli of 500 ms duration were presented, and the responses were displayed as peristimulus time histograms. These histograms showed regular peaks, indicating a “chopping” pattern of response. The rate during each chopping period as well as the general trend of the histogram could be well fit by an equation that expresses the firing rate as a sum of 1) a short-term adaptive rate that decays exponentially with time and 2) a constant steady-state rate. For the adaptation in medial olivocochlear (MOC) neurons, the average exponential time constant was 47 ms, which is roughly similar to that for short-term adaptation in auditory-nerve fibers. The amount of adaptation (expressed as a percentage decrease of onset firing rate), however, was substantially less in MOC neurons (average 31%) than in auditory-nerve fibers (average 63%). To test for adaptation over longer periods, we used noise and tones of 10 s duration. After the short-term adaptation, the responses of MOC neurons were almost completely sustained (average long-term adaptation 3%). However, in the same preparations, significant long-term adaptation was present in auditory-nerve fibers. These results indicate that the MOC response adaptation is minimal compared with that of auditory-nerve fibers. Such sustained responses may enable the MOC system to produce sustained effects in the periphery, supporting a role for this efferent system during ongoing stimuli of long duration.
Apical and Basal Orthodromic Population Spikes in Hippocampal CA1 In Vivo Show Different Origins and Patterns of Propagation
Authors: Kloosterman Fabian , Peloquin Pascal , Leung L. Stan
Published: December 2017

There is controversy concerning whether orthodromic action potentials originate from the apical or basal dendrites of CA1 pyramidal cells in vivo. The participation of the dendrites in the initialization and propagation of population spikes in CA1 of urethan-anesthetized rats in vivo was studied using simultaneously recorded field potentials and current source density (CSD) analysis. CSD analysis revealed that the antidromic population spike, evoked by stimulation of the alveus, invaded in succession, the axon initial segment (stratum oriens), cell body and ∼200 μm of the proximal apical dendrites. Excitation of the basal dendrites of CA1, following stimulation of CA3 stratum oriens, evoked an orthodromic spike that started near the cell body or initial segment and then propagated ∼200 μm into the proximal apical dendrites. In contrast, the population spike that followed excitation of the apical dendrites of CA1 initiated at the proximal apical dendrites, 50–100 μm distal to the cell body layer, and then propagated centripetally to the cell body and the proximal basal dendrites. A late apical dendritic spike may arise in the mid-apical dendrites (250–300 μm from the cell layer) and propagated distally. The origin or the pattern of propagation of each population spike type was similar for near-threshold to supramaximal stimulus intensities. In summary, population spikes following apical dendritic and basal dendritic excitation in vivo appeared to originate from different locations. Apical dendritic excitation evoked a population spike that initiated in the proximal apical dendrites while basal dendritic excitation evoked a spike that started near the initial segment or cell body. An original finding of this study is the propagation of the population spike from basal to apical dendrites in vivo or vice versa. This backpropagation from one dendritic tree to the other may play an important role in the synaptic plasticity among a network of CA3 to CA1 neurons.
Spatiotemporal Properties of an Evoked Population Activity in Rat Sensory Cortical Slices
Authors: Wu Jian-Young , Guan Li , Bai Li , Yang Qian
Published: December 2017

We have examined the spatiotemporal properties of ensemble activity, an evoked all-or-none polysynaptic activity in rat neocortical slices. Ensemble activity occurred in cortical slices bathed in normal artificial cerebrospinal fluid (ACSF) and was evoked by a single electrical shock either to the white matter or directly to the cortical tissue. This activity was seen in slices of somatosensory and auditory cortices; in other cortical areas we have not been able to evoke it. The activity developed 10 to 250 ms poststimulus and lasted 280 ± 120 ms in local field potential (LFP) recordings. Voltage-sensitive dye imaging showed that this activity was an area of activation 0.8 ± 0.4 mm wide that propagated slowly (11.4 ± 6.2 mm/s, n = 60, 6 animals) in the horizontal direction. Due to this propagation, the actual duration in the whole tissue may be longer (∼400 ms) than that recorded by a single LFP electrode. Ensemble activity produced a low-amplitude optical signal (7–14% of the interictal-like spikes in the same tissue), suggesting a moderate net depolarization of the population. These were very different from hyperexcitable (epileptiform) events in the same tissue that had about 10 times the optical signal amplitude and propagated at 125 ± 24 mm/s ( n = 21, 6 animals). On a global spatial scale (∼0.8 mm wide in layers II–III) ensemble activity had a smooth waveform in voltage-sensitive dye signals (population transmembrane potential). On a local scale, field potential recordings showed large fluctuations with complex oscillations and substantial trial-to-trial variation. This suggests that oscillations in cortical circuits occurred only in small clusters of correlated neurons. Ensemble activity was sensitive to the excitation-inhibition balance of the local network. Antagonists of N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and GABAa receptors, and muscarinic agonists and other modest manipulations such as increasing bath concentration of Mg2+ to 2.5–4 mM (normally at 2 mM), or K+ to 5–7 mM (normally 3 mM), all significantly reduced the probability of evoking the activity. The metabotropic glutamate receptor agonist, aminocyclopentane-1,3-dicarboxylic acid, blocked the activity at a low concentration (10–15 μM), while the antagonist (R,S)-α-methyl-4-carboxyphenylglycine had no effect even at high concentration (240 μM). Our data suggest that locally organized neuronal clusters may play a role in the organization of oscillatory activities in the gamma band and may participate in cortical integration/amplification occurring on a scale of ∼1 mm × 300 ms.
Prolonged Bursts Occur in Normal Calcium in Hippocampal Slices After Raising Excitability and Blocking Synaptic Transmission
Authors: Xiong Zhi-Qi , Stringer Janet L.
Published: December 2017

This study examined the conditions that are required for the appearance of the long-duration seizure-like activity that can be recorded in hippocampal slices. Spontaneous interictal activity was induced in CA1 and CA3 by perfusing hippocampal slices with high potassium, cesium, 4-aminopyridine, or tetraethylammonium chloride, in normal levels of calcium. Synaptic transmission was then blocked by the addition of neurotransmitter receptor blockers (6-cyano-7-nitroquinoxaline-2,3-dione,d,l-2-amino-5-phosphonopentanoic acid, and bicuculline) or the calcium channel blocker cadmium, resulting in complete blockade of the interictal discharges and the appearance of spontaneous seizure-like events (ictal-like discharges) primarily in CA1 and the dentate gyrus. Blocking synaptic transmission in normal artificial cerebrospinal fluid did not induce ictal-like discharges in any region. The results demonstrate that ictal-like discharges can appear in normal levels of extracellular calcium when chemical synaptic transmission is blocked pharmacologically. The results suggest that an increase in neuronal excitability and absence of interictal activity promote the appearance of the longer ictal-like discharges.
Mechanisms Underlying the Sensitivity of Neurons in the Lateral Superior Olive to Interaural Intensity Differences
Authors: Irvine D.R.F. , Park V. N. , McCormick L.
Published: December 2017

The initial processing of interaural intensity differences (IIDs), the major cue to the azimuthal location of high-frequency sounds in mammals, is carried out by neurons in the lateral superior olivary nucleus (LSO) that receive excitatory input from the ipsilateral ear and inhibitory input from the contralateral ear (IE neurons). The “latency” hypothesis asserts that it is the effects of intensity differences on the latency, and hence the relative timing, of the synaptic inputs to these neurons that is the basis of their sensitivity to IIDs, while other models assign the major role to changes in the relative amplitude of the inputs. To test the latency hypothesis and to determine the contributions of changes in the relative timing and amplitude of synaptic inputs to the IID sensitivity of LSO neurons, a method was developed of generating sets of stimuli that produced either the same changes in the relative timing of inputs without any change in their amplitude (equivalent interaural time difference stimuli) or the same differences in amplitude without any difference in timing (delay-cancelled IID stimuli) as a given range of IIDs. Data were obtained from a sample of IE neurons in the LSO of anesthetized rats using these stimulus paradigms and click and tone-burst stimuli. For click stimuli, the IID sensitivity of a small proportion of neurons was explained entirely by sensitivity to differences in input timing, but the sensitivity of most neurons reflected either sensitivity to the relative amplitude of inputs or to the joint operation of both factors. In neurons whose sensitivity was tested at a number of different absolute sound pressure levels (SPLs), the relative contributions of the two factors tended to differ at different SPLs. The IID sensitivity of onset responses to tone stimuli could be classified into the same three categories but was explained for a larger proportion of neurons by sensitivity to differences in input timing. The IID sensitivity of the late response component of neurons with sustained responses to tones in all cases reflected sensitivity to the relative amplitude of the inputs. The results confirm the contribution of changes in latency produced by intensity changes to the IID sensitivity of the onset responses of many IE neurons in LSO but require rejection of the strong form of the latency hypothesis, which asserts that this factor alone accounts for such sensitivity.
B2 Receptor–Mediated Enhanced Bradykinin Sensitivity of Rat Cutaneous C-Fiber Nociceptors During Persistent Inflammation
Authors: Banik Ratan Kumar , Kozaki Yasuko , Sato Jun , Gera Lajos , Mizumura Kazue
Published: December 2017

Bradykinin (BK), which has potent algesic and sensitizing effect on nociceptors, is of current interest in understanding the mechanisms of chronic pain. BK response is mediated by B2 receptor in normal conditions; however, findings that B1 receptor blockade alleviated hyperalgesia in inflammation have been highlighting the role of B1 receptor in pathological conditions. It has not yet been clear whether nociceptor activities are modified by B1 receptor agonists or antagonists during inflammation. In addition, previous studies reported the change in BK sensitivity of nociceptors during short-lasting inflammation, and data in persistent inflammation are lacking. Therefore we investigated whether an experimentally induced persistent inflammatory state modulates the BK sensitivity of nociceptors and which receptor subtype plays a more important role in this condition. Complete Freund's adjuvant was injected into the rat-tail and after 2–3 wk, persistent inflammation developed, which was prominent in the ankle joint. Using an in vitro skin-saphenous nerve preparation, single-fiber recordings were made from mechano-heat sensitive C-fiber nociceptors innervating rat hairy hindpaw skin, and their responses were compared with those obtained from C-fibers tested similarly in normal animals. BK at 10−8 M excited none of the 10 C-fibers in normal animals while it excited 5 of 11 (45%) C-fibers of inflamed animals, and at 10−6 M BK excited all of the 11 inflamed C-fibers (or 94% of 36 tested C-fibers) but only 4 of 10 (or 45% of 58 tested C-fibers) in normal animals. Thus the concentration-response curves based on the incidence of BK induced excitation, and the total number of impulses evoked in response to BK were significantly shifted to the left. Moreover, an increased percentage of the inflamed C-fibers responded to 10−6 M BK with bursting or high-frequency discharges. Thirty-percent of inflamed C-fibers had spontaneous activity, and these fibers showed comparatively less tachyphylaxis to consecutive second and third 10−6 M BK stimulation. A B2 receptor antagonist (d-Arg-[Hyp3, Thi5,8,d-phe7]-BK) completely eliminated BK responses in inflamed rats, while B1 receptor antagonists (B 9958 and Des-Arg9-[Leu8]-BK) had no effect. Selective B1 receptor agonist (Des-Arg10-Kallidin) excited 46% ( n = 13) of inflamed C-fibers at 10−5 M concentration, which is 1,000 times higher than that of BK needed to excite the same percentage of inflamed C-fibers. We conclude that in chronically inflamed tissue, sensitivity of C-fiber nociceptors to BK, which is B2 receptor mediated, is strongly increased and that B1 receptor may not be important to a persistent inflammatory state, at least at the primary afferent level.
Statistical Model Relating CA3 Burst Probability to Recovery From Burst-Induced Depression at Recurrent Collateral Synapses
Authors: Staley Kevin J. , Bains Jaideep S. , Yee Audrey , Hellier Jennifer , Longacher J. Mark
Published: December 2017

When neuronal excitability is increased in area CA3 of the hippocampus in vitro, the pyramidal cells generate periodic bursts of action potentials that are synchronized across the network. We have previously provided evidence that synaptic depression at the excitatory recurrent collateral synapses in the CA3 network terminates each population burst so that the next burst cannot begin until these synapses have recovered. These findings raise the possibility that burst timing can be described in terms of the probability of recovery of this population of synapses. Here we demonstrate that when neuronal excitability is changed in the CA3 network, the mean and variance of the interburst interval change in a manner that is consistent with a timing mechanism comprised of a pool of exponentially relaxing pacemakers. The relaxation time constant of these pacemakers is the same as the time constant describing the recovery from activity-dependent depression of recurrent collateral synapses. Recovery was estimated from the rate of spontaneous transmitter release versus time elapsed since the last CA3 burst. Pharmacological and long-term alterations of synaptic strength and network excitability affected CA3 burst timing as predicted by the cumulative binomial distribution if the burst pace-maker consists of a pool of recovering recurrent synapses. These findings indicate that the recovery of a pool of synapses from burst-induced depression is a sufficient explanation for burst timing in the in vitro CA3 neuronal network. These findings also demonstrate how information regarding the nature of a pacemaker can be derived from the temporal pattern of synchronous network activity. This information could also be extracted from less accessible networks such as those generating interictal epileptiform discharges in vivo.