bluuebunny/crossref_metadata_2025 huggingface dataset:
Contact-Evoked Changes in EMG Activity During Human Grasp
Authors: Collins D. F. , Knight B. , Prochazka A.
Published: December 2017

Contact-evoked changes in EMG activity during human grasp. 2215 Cutaneous receptors in the digits discharge bursts of activity on contact with an object during human grasp. In this study, we investigated the contribution of this sensory activity to the responses of muscles involved in the task. Twelve subjects performed a standardized precision grasp task without the aid of vision. Electromyographic (EMG) responses in trials when the object was present were compared with those in which the object, and hence the associated afferent responses, were unexpectedly absent. Significant differences in EMG amplitude occurred in the interval 50–100 ms after contact in all subjects and in 33/46 of the muscles sampled. The differences emerged as early as 34 ms after contact and comprised as much as a fourfold change in EMG from 50 to 100 ms after contact with the object. Typically, EMG responses were larger when the object was present (OP), though there were cases, particularly in the thenar muscles, in which the responses increased when the object was absent (OA). Local anesthesia of the thumb and index finger attenuated contact-evoked EMG activity in at least one muscle in all four subjects tested. In one subject, contact-evoked responses were abolished completely during the anesthesia in all four muscles sampled. The results indicate that the sensory activity signaling contact plays a key role in regulating EMG activity during human grasp. Much of this feedback action is attributable to cutaneous receptors in the digits and probably involves both spinal and supraspinal pathways.
Perturbation of Combined Saccade-Vergence Movements by Microstimulation in Monkey Superior Colliculus
Authors: Chaturvedi Vivek , van Gisbergen Jan A. M.
Published: December 2017

Perturbation of combined saccade-vergence movements by microstimulation in monkey superior colliculus. This study investigated the role of the monkey superior colliculus (SC) in the control of visually (V)-guided combined saccade-vergence movements by assessing the perturbing effects of microstimulation. We elicited an electrical saccade (E) by stimulation (in 20% of trials) in the SC while the monkey was preparing a V-guided movement to a near target. The target was aligned such that E- and V-induced saccades had similar amplitudes but different directions and such that V-induced saccades had a significant vergence component (saccades to a near target). The onset of the E-stimulus was varied from immediately after V-target onset to after V-saccade onset. E-control trials, where stimulation was applied during fixation of a V-target, yielded the expected saccade but no vergence. By contrast, early perturbation trials, where the E-stimulus was applied soon after the onset of the V-target, caused an E-triggered response with a clear vergence component toward the V-target. Midflight perturbation, timed to occur just after the monkey initiated the movement toward the target, markedly curtailed the ongoing vergence component during the saccade. Examination of pooled responses from both types of perturbation trials showed weighted-averaging effects between E- and V-stimuli in both saccade and fast vergence components. Both components exhibited a progression from E- to V-dominance as the E-stimulus was delayed further. This study shows that artificial intervention in the SC, while a three-dimensional (3D) refixation is being prepared or is ongoing, can affect the timing (when) and the metric specification (where) of both saccades and vergence. To explain this we interpret the absence of overt vergence in the E-controls as being caused by a zero-vergence change command rather than reflecting the mere absence of a collicular vergence signal. In the perturbation trials, the E-evoked zero-vergence signal competes with the V-initiated saccade-vergence signal, thereby giving rise to a compromised 3D response. This effect would be expected if the population of movement cells at each SC site is tuned in 3D, combining the well-known topographical code for direction and amplitude with a nontopographical depth representation. On E-stimulation, the local population would yield a net saccade signal caused by the topography, but the cells coding for different depths would be excited equally, causing the vergence change to be zero.
Vertical Eye Position–Dependence of the Human Vestibuloocular Reflex During Passive and Active Yaw Head Rotations
Authors: Thurtell Matthew J. , Black Ross A. , Halmagyi G. Michael , Curthoys Ian S. , Aw Swee T.
Published: December 2017

Vertical eye position–dependence of the human vestibuloocular reflex during passive and active yaw head rotations. The effect of vertical eye-in-head position on the compensatory eye rotation response to passive and active high acceleration yaw head rotations was examined in eight normal human subjects. The stimuli consisted of brief, low amplitude (15–25°), high acceleration (4,000–6,000°/s2) yaw head rotations with respect to the trunk (peak velocity was 150–350°/s). Eye and head rotations were recorded in three-dimensional space using the magnetic search coil technique. The input-output kinematics of the three-dimensional vestibuloocular reflex (VOR) were assessed by finding the difference between the inverted eye velocity vector and the head velocity vector (both referenced to a head-fixed coordinate system) as a time series. During passive head impulses, the head and eye velocity axes aligned well with each other for the first 47 ms after the onset of the stimulus, regardless of vertical eye-in-head position. After the initial 47-ms period, the degree of alignment of the eye and head velocity axes was modulated by vertical eye-in-head position. When fixation was on a target 20° up, the eye and head velocity axes remained well aligned with each other. However, when fixation was on targets at 0 and 20° down, the eye velocity axis tilted forward relative to the head velocity axis. During active head impulses, the axis tilt became apparent within 5 ms of the onset of the stimulus. When fixation was on a target at 0°, the velocity axes remained well aligned with each other. When fixation was on a target 20° up, the eye velocity axis tilted backward, when fixation was on a target 20° down, the eye velocity axis tilted forward. The findings show that the VOR compensates very well for head motion in the early part of the response to unpredictable high acceleration stimuli—the eye position– dependence of the VOR does not become apparent until 47 ms after the onset of the stimulus. In contrast, the response to active high acceleration stimuli shows eye position–dependence from within 5 ms of the onset of the stimulus. A model using a VOR-Listing’s law compromise strategy did not accurately predict the patterns observed in the data, raising questions about how the eye position–dependence of the VOR is generated. We suggest, in view of recent findings, that the phenomenon could arise due to the effects of fibromuscular pulleys on the functional pulling directions of the rectus muscles.
Influence of Previous Visual Stimulus or Saccade on Saccadic Reaction Times in Monkey
Authors: Dorris Michael C. , Taylor Tracy L. , Klein Raymond M. , Munoz Douglas P.
Published: December 2017

Influence of previous visual stimulus or saccade on saccadic reaction times in monkey. Saccadic reaction times (SRTs) to suddenly appearing targets are influenced by neural processes that occur before and after target presentation. The majority of previous studies have focused on how posttarget factors, such as target attributes or changes in task complexity, affect SRTs. Studies of pretarget factors have focused on how prior knowledge of the timing or location of the impending target, gathered through cueing or probabilistic information, affects SRTs. Our goal was to investigate additional pretarget factors to determine whether SRTs can also be influenced by the history of saccadic and visual activity even when these factors are spatially unpredictive as to the location of impending saccadic targets. Monkeys were trained on two paradigms. In the saccade-saccadeparadigm, monkeys were required to follow a saccadic target that stepped from a central location, to an eccentric location, back to center, and finally to a second eccentric location. The stimulus-saccade paradigm was similar, except the central fixation target remained illuminated during presentation of the first eccentric stimulus; the monkey was required to maintain central fixation and to make a saccade to the second eccentric stimulus only on disappearance of the fixation point. In both paradigms, the first eccentric stimulus was presented at the same, opposite, or orthogonal location with respect to the final target location in a given trial. We measured SRTs to the final target under conditions in which all parameters were identical except for the location of the first eccentric stimulus. In the saccade-saccade paradigm, we found that the SRT to the final target was slowest when it was presented opposite to the initial saccadic target, whereas in the stimulus-saccade paradigm the SRT to the final target was slowest when it was presented at the same location as the initial stimulus. In both paradigms, these increases in SRTs were greatest during the shortest intervals between presentation of successive eccentric stimuli, yet these effects remained present for the longest intervals employed in this study. SRTs became faster as the direction and eccentricity of the two successive stimuli became increasingly misaligned from that which produced the maximal SRT slowing in each paradigm. The results of the stimulus-saccade paradigm are similar to the phenomenon of inhibition of return (IOR) in which human subjects are slower to respond to stimuli that are presented at previously cued locations. We interpret these findings in terms of overlapping representations of visuospatial and oculomotor activity in the same neural structures.
Neural Correlates of Gap Detection in Three Auditory Cortical Fields in the Cat
Authors: Eggermont Jos J.
Published: December 2017

Neural correlates of gap detection in three auditory cortical fields in the cat. Mimimum detectable gaps in noise in humans are independent of the position of the gap, whereas in cat primary auditory cortex (AI) they are position dependent. The position dependence in other cortical areas is not known and may resolve this contrast. This study presents minimum detectable gap-in-noise values for which single-unit (SU), multiunit (MU) recordings and local field potentials (LFPs) show an onset response to the noise after the gap. The gap, which varied in duration between 5 and 70 ms, was preceded by a noise burst of either 5 ms (early gap) or 500 ms (late gap) duration. In 10 cats, simultaneous recordings were made with one electrode each in AI, anterior auditory field (AAF), and secondary auditory cortex (AII). In nine additional cats, two electrodes were inserted in AI and one in AAF. Minimum detectable gaps based on SU, MU, or LFP data in each cortical area were the same. In addition, very similar minimum early-gap values were found in all three areas (means, 36.1–41.7 ms). The minimum late-gap values were also similar in AI and AII (means, 11.1 and 11.7 ms), whereas AAF showed significantly larger minimum late-gap durations (mean 21.5 ms). For intensities >35 dB SPL, distributions of minimum early-gap durations in AAF and AII had modal values at ∼45 ms. In AI, the distribution was more uniform. Distributions for minimum late-gap duration were skewed toward low values (mode at 5 ms), but high values (≤60 ms) were found infrequently as well. A small fraction of units showed a response after the gap only for early-gap durations <20 ms. In AI and AII, the mean minimum early- and late-gap durations decreased significantly with increase in the neuron’s characteristic frequency (CF), whereas the lower boundary for the minimum early gap was CF independent. The findings suggest that human within-perceptual-channel gap detection, showing no dependence of the minimum detectable gap on the duration of the leading noise burst, likely is based on the lower envelope of the distribution of neural minimum gap values of units in AI and AAF. In contrast, across-perceptual-channel gap detection, which shows a decreasing minimum detectable gap with increasing duration of the leading noise burst, likely is based on the comparison ofon responses from populations of neurons that converge on units in AII.
Role of [Ca2+]iin the ATP-Induced Heat Sensitization Process of Rat Nociceptive Neurons
Authors: Kress M. , Guenther S.
Published: December 2017

Role of [Ca2+]iin the ATP-induced heat sensitization process of rat nociceptive neurons. In inflamed tissue, nociceptors show increased sensitivity to noxious heat, which may account for heat hyperalgesia. In unmyelinated nociceptive afferents in rat skin in vitro, a drop of heat threshold and an increase in heat responses were induced by experimental elevation of intracellular calcium ([Ca2+]i) levels with the calcium ionophore ionomycin (10 μM). Similar results were obtained in experiments employing [Ca2+]irelease from preloaded “caged calcium” (NITR-5/AM) via UV photolysis. In both cases, sensitization was prevented by preventing rises in [Ca2+]iwith the membrane-permeant calcium chelator BAPTA-AM (1 mM). No pronounced change of mechanical sensitivity was observed. Heat-induced membrane currents ( Iheat) were investigated with patch-clamp recordings, and simultaneous calcium measurements were performed in small sensory neurons isolated from adult rat dorsal root ganglia (DRG). Ionomycin-induced rises in [Ca2+]iresulted in reversible sensitization of Iheat. In the same subset of DRG neurons, the endogenous algogen ATP (100 μM) was used to elevate [Ca2+]i, which again resulted in significant sensitization of Iheat. In correlative recordings from the skin–nerve preparation, ATP induced heat sensitization of nociceptors, which again could be blocked by preincubation with BAPTA-AM. Rises in [Ca2+]iin response to inflammatory mediators, e.g., ATP, thus appear to play a central role in plastic changes of nociceptors, which may account for hypersensitivity of inflamed tissue.
Sag During Unfused Tetanic Contractions in Rat Triceps Surae Motor Units
Authors: Carp J. S. , Herchenroder P. A. , Chen X. Y. , Wolpaw J. R.
Published: December 2017

Sag during unfused tetanic contractions in rat triceps surae motor units. Contractile properties and conduction velocity were studied in 202 single motor units of intact rat triceps surae muscles activated by intra-axonal (or intra-myelin) current injection in L5 or L6 ventral root to assess the factors that determine the expression of sag (i.e., decline in force after initial increase during unfused tetanic stimulation). Sag was consistently detected in motor units with unpotentiated twitch contraction times <20 ms. However, the range of frequencies at which sag was expressed varied among motor units such that there was no single interstimulus interval (ISI), with or without adjusting for twitch contraction time, at which sag could be detected reliably. Further analysis indicated that using the absence of sag as a criterion for identifying slow-twitch motor units requires testing with tetani at several different ISIs. In motor units with sag, the shape of the force profile varied with tetanic frequency and contractile properties. Simple sag force profiles (single maximum reached late in the tetanus followed by monotonic decay) tended to occur at shorter ISIs and were observed more frequently in fatigue-resistant motor units with long half-relaxation times and small twitch amplitudes. Complex sag profiles reached an initial maximum early in the tetanus, tended to occur at longer ISIs, and were more common in fatigue-sensitive motor units with long half-relaxation times and large twitch amplitudes. The differences in frequency dependence and force maximum location suggested that these phenomena represented discrete entities. Successive stimuli elicited near-linear increments in force during tetani in motor units that never exhibited sag. In motor units with at least one tetanus displaying sag, tetanic stimulation elicited large initial force increments followed by rapidly decreasing force increments. That the latter force envelope pattern occurred in these units even in tetani without sag suggested that the factors responsible for sag were expressed in the absence of overt sag. The time-to-peak force (TTP) of the individual contractions during a tetanus decreased in tetani with sag. Differences in the pattern of TTP change during a tetanus were consistent with the differences in force maximum location between tetani exhibiting simple and complex sag. Tetani from motor units that never exhibited sag did not display a net decrease in TTP during successive contractions. These data were consistent with the initial force decrement of sag resulting from a transient reduction in the duration of the contractile state.
Both External and Internal Calcium Reduce the Sensitivity of the Olfactory Cyclic-Nucleotide-Gated Channel tocAMP
Authors: Kleene Steven J.
Published: December 2017

Both external and internal calcium reduce the sensitivity of the olfactory cyclic-nucleotide-gated channel to cAMP. In vertebrate olfaction, odorous stimuli are first transduced into an electrical signal in the cilia of olfactory receptor neurons. Many odorants cause an increase in ciliary cAMP, which gates cationic channels in the ciliary membrane. The resulting influx of Ca2+and Na+produces a depolarizing receptor current. Modulation of the cyclic-nucleotide-gated (CNG) channels is one mechanism of adjusting olfactory sensitivity. Modulation of these channels by divalent cations was studied by patch-clamp recording from single cilia of frog olfactory receptor neurons. In accord with previous reports, it was found that cytoplasmic Ca2+above 1 μM made the channels less sensitive to cAMP. The effect of cytoplasmic Ca2+was eliminated by holding the cilium in a divalent-free cytoplasmic solution and was restored by adding calmodulin (CaM). An unexpected result was that external Ca2+could also greatly reduce the sensitivity of the channels to cAMP. This reduction was seen when external Ca2+exceeded 30 μM and was not affected by the divalent-free solution, by CaM, or by Ca2+buffering. The effects of cytoplasmic and external Ca2+were additive. Thus the effects of cytoplasmic and external Ca2+are apparently mediated by different mechanisms. There was no effect of CaM on a Ca2+-activated Cl−current that also contributes to the receptor current. Increases in Ca2+concentration on either side of the ciliary membrane may influence olfactory adaptation.
Upregulation of Calcium Homeostatic Mechanisms in Chronically Depolarized Rat Myenteric Neurons
Authors: Fickbohm David J. , Willard Alan L.
Published: December 2017

Upregulation of calcium homeostatic mechanisms in chronically depolarized rat myenteric neurons. Perturbations of intracellular Ca2+ion concentration ([Ca2+]i) have important effects on numerous neuronal processes and influence development and survival. Neuronal [Ca2+]iis, in large part, dependent on activity, and changes in activity levels can alter how neurons handle calcium (Ca). To investigate the ability of neuronal Ca homeostatic mechanisms to adapt to the persistent elevation of [Ca2+]i, we used optical and electrophysiological recording techniques to measure [Ca2+]itransients in neurons from the rat myenteric plexus that had been chronically depolarized by growth in culture medium containing elevated (25 mM) KCl. When studied in normal saline, neurons that had previously been chronically depolarized for 3–5 days had briefer action potentials than control neurons, their action potentials produced smaller, more rapidly decaying increases in [Ca2+]i, and voltage-clamp pulses with action potential waveforms evoked smaller Ca currents than in control neurons. Simultaneous voltage-clamp measurements and calcium imaging revealed that increases in the Ca handling capacities of the chronically depolarized neurons permitted them to limit the amplitudes of action potential-evoked [Ca2+]itransients and to restore [Ca2+]ito basal levels more rapidly than control neurons. Release of Ca from endoplasmic reticulum-based Ca stores made smaller contributions to action potential-evoked [Ca2+]itransients in chronically depolarized neurons even though those neurons had larger caffeine-releasable Ca stores. Endoplasmic reticulum-based Ca sequestration mechanisms appeared to contribute to the faster decay of [Ca2+]itransients in chronically depolarized neurons. These results demonstrate that when neurons experience prolonged perturbations of [Ca2+]i, they can adjust multiple components of their Ca homeostatic machinery. Appropriate utilization of this adaptive capability should help neurons resist potentially lethal metabolic and environmental insults.
Testing the Classification of Static γ Axons Using Different Patterns of Random Stimulation
Authors: Petit Julien , Banks Robert W. , Laporte Yves
Published: December 2017

Testing the classification of static γ axons using different patterns of random stimulation. The possibility of using randomly generated stimulus intervals (with a Poisson distribution) to identify the type(s) of intrafusal fiber activated by the stimulation of single static γ axons was tested in Peroneus tertius muscle spindles of anesthetized cats. Three patterns of random stimulation with different values of mean intervals [20 ± 4.47, 30 ± 8.94, and 40 ± 8.94 (SD) ms] were used. Single static γ axons activating, in single spindles, either the bag2 fiber alone or the chain fibers alone or both types of intrafusal fiber were prepared. Responses of spindle primary endings elicited by the stimulation of γ axons were recorded from Ia fibers in cut dorsal root filaments. Cross-correlograms between stimuli and spikes of the primary ending responses, autocorrelograms, interval histograms of responses, and stimulations were built. The characteristics of cross-correlograms were found to be related not only to the type of intrafusal muscle fibers activated but also to the parameters of the stimulation. Moreover some cross-correlograms with similar characteristics were produced by the activation of different intrafusal muscle fibers. It also was observed that, whatever the type of intrafusal muscle fiber activated, cross-correlograms could exhibit oscillations after an initial peak, provided the extent in frequency of the primary ending response was small; these oscillations arise in part from the autocorrelation of the primary ending responses. Therefore, cross-correlograms obtained during random stimulation of static γ axons cannot be used for unequivocally identifying the type(s) of intrafusal muscle fiber these axons supply.
Maturation of Neuromuscular Transmission During Early Development in Zebrafish
Authors: Nguyen Peter V. , Aniksztejn Laurent , Catarsi Stefano , Drapeau Pierre
Published: December 2017

Maturation of neuromuscular transmission during early development in zebrafish. We have examined the rapid development of synaptic transmission at the neuromuscular junction (NMJ) in zebrafish embryos and larvae by patch-clamp recording of spontaneous miniature endplate currents (mEPCs) and single acetylcholine receptor (AChR) channels. Embryonic (24–36 h) mEPCs recorded in vivo were small in amplitude (<50 pA). The rate of mEPCs increased in larvae (3.5-fold increase measured by 6 days), and these mEPCs were mostly of larger amplitude (10-fold on average) with (≤5-fold) faster kinetics. Intracellular labeling with Lucifer yellow indicated extensive coupling between muscle cells in both embryos and larvae (≤10 days). Blocking acetylcholinesterase (AChE) with eserine had no effect on mEPC kinetics in embryos at 1 day and only partially slowed (by ∼½) the decay rate in larvae at 6 days. In acutely dissociated muscle cells, we observed the same two types of AChR with conductances of 45 and 60 pS and with similar, brief (<0.5 ms) mean open times in both embryos and larvae. We conclude that AChR properties are set early during development at these early stages; functional maturation of the NMJ is only partly shaped by expression of AChE and may also depend on postsynaptic AChR clustering and presynaptic maturation.
Physiological Properties of Neurons in the Ventral Nucleus of the Lateral Lemniscus of the Rat: Intrinsic Membrane Properties and Synaptic Responses
Authors: Wu Shu Hui
Published: December 2017

Physiological properties of neurons in the ventral nucleus of the lateral lemniscus of the rat: intrinsic membrane properties and synaptic responses. The physiological properties including current-voltage relationships, firing patterns, and synaptic responses of the neurons in the ventral nucleus of the lateral lemniscus (VNLL) were studied in brain slices taken through the young rat’s (17–37 days old) auditory brain stem. Intracellular recordings were made from VNLL neurons, and synaptic potentials were elicited by electrical stimulation of the lateral lemniscus ventral to the VNLL. Current-voltage relations and firing patterns were tested by recording the electrical potentials produced by intracellular injection of positive and negative currents. There were two types of VNLL neurons (type I and II) that exhibited different current-voltage relationships. In response to negative current, both type I and II neurons produced a graded hyperpolarization. Type I neurons responded to positive current with a graded depolarization and multiple action potentials the number of which was related to the strength of the current injected. The current-voltage relations of type I neurons were nearly linear. Type II neurons responded to positive current with a limited depolarization and only one or a few action potentials. The current-voltage relations of type II neurons were nonlinear near the resting potential. The membrane properties of the type II VNLL neurons may play an important role for processing information about time of onset of a sound. Type I neurons showed three different firing patterns, i.e., regular, onset-pause and adaptation, in response to small positive current. The onset-pause and adaptation patterns could become sustained when a large current was injected. The regular, onset-pause, and adaptation patterns in type I neurons and the onset pattern in type II neurons resemble “chopper,” “pauser,” “primary-like,” and “on” responses, respectively, as defined in in vivo VNLL studies. The results suggest that different responses to acoustic stimulation could be attributed to intrinsic membrane properties of VNLL neurons. Many VNLL neurons responded to stimulation of the lateral lemniscus with excitatory or inhibitory responses or both. Excitatory and inhibitory responses showed interaction, and the output of the synaptic integration depended on the relative strength of excitatory and inhibitory responses. Neurons with an onset-pause firing pattern were more likely to receive mixed excitatory and inhibitory inputs from the lower auditory brain stem.
Group I mGluR Activation Causes Voltage-Dependent and -Independent Ca2+Rises in Hippocampal Pyramidal Cells
Authors: Bianchi Riccardo , Young Steven R. , Wong Robert K. S.
Published: December 2017

Group I mGluR activation causes voltage-dependent and -independent Ca2+rises in hippocampal pyramidal cells. Application of the metabotropic glutamate receptor (mGluR) agonist (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) or the selective group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) depolarized both CA3 and CA1 pyramidal cells in guinea pig hippocampal slices. Simultaneous recordings of voltage and intracellular Ca2+levels revealed that the depolarization was accompanied by a biphasic elevation of intracellular Ca2+concentration ([Ca2+]i): a transient calcium rise followed by a delayed, sustained elevation. The transient [Ca2+]irise was independent of the membrane potential and was blocked when caffeine was added to the perfusing solution. The sustained [Ca2+]irise appeared when membrane depolarization reached threshold for voltage-gated Ca2+influx and was suppressed by membrane hyperpolarization. The depolarization was associated with an increased input resistance and persisted when either the transient or sustained [Ca2+]iresponses was blocked. mGluR-mediated voltage and [Ca2+]iresponses were blocked by (+)-α-methyl-4-carboxyphenylglycine (MCPG) or ( S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG). These data suggest that in both CA3 and CA1 hippocampal cells, activation of group I mGluRs produced a biphasic accumulation of [Ca2+]ivia two paths: a transient release from intracellular stores, and subsequently, by influx through voltage-gated Ca2+channels. The concurrent mGluR-induced membrane depolarization was not caused by the [Ca2+]irise.
Reciprocal Synaptic Interactions Between Rod Bipolar Cells and Amacrine Cells in the Rat Retina
Authors: Hartveit Espen
Published: December 2017

Reciprocal synaptic interactions between rod bipolar cells and amacrine cells in the rat retina. Reciprocal synaptic transmission between rod bipolar cells and presumed A17 amacrine cells was studied by whole cell voltage-clamp recording of rod bipolar cells in a rat retinal slice preparation. Depolarization of a rod bipolar cell evoked two identifiable types of Ca2+ current, a T-type current that activated at about −70 mV and a current with L-type pharmacology that activated at about −50 mV. Depolarization to greater than or equal to −50 mV also evoked an increase in the frequency of postsynaptic currents (PSCs). The PSCs reversed at ∼ E Cl (the chloride equilibrium potential), followed changes in E Cl, and were blocked by γ-aminobutyric acidA (GABAA) and GABAC receptor antagonists and thus were identified as GABAergic inhibitory PSCs (IPSCs). Bipolar cells with cut axons displayed the T-type current but lacked an L-type current and depolarization-evoked IPSCs. Thus L-type Ca2+ channels are placed strategically at the axon terminals to mediate transmitter release from rod bipolar cells. The IPSCs were blocked by the non- N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, indicating that non-NMDA receptors mediate the feed-forward bipolar-to-amacrine excitation. The NMDA receptor antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid had no consistent effect on the depolarization-evoked IPSCs, indicating that activation of NMDA receptors is not essential for the feedforward excitation. Tetrodotoxin (a blocker of voltage-gated Na+channels) reversibly suppressed the reciprocal response in some cells but not in others, indicating that graded potentials are sufficient for transmitter release from A17 amacrine cells, but suggesting that voltage-gated Na+ channels, under some conditions, can contribute to transmitter release.
Stochastic Nature of Precisely Timed Spike Patterns in Visual System Neuronal Responses
Authors: Oram M. W. , Wiener M. C. , Lestienne R. , Richmond B. J.
Published: December 2017

Stochastic nature of precisely timed spike patterns in visual system neuronal responses. It is not clear how information related to cognitive or psychological processes is carried by or represented in the responses of single neurons. One provocative proposal is that precisely timed spike patterns play a role in carrying such information. This would require that these spike patterns have the potential for carrying information that would not be available from other measures such as spike count or latency. We examined exactly timed (1-ms precision) triplets and quadruplets of spikes in the stimulus-elicited responses of lateral geniculate nucleus (LGN) and primary visual cortex (V1) neurons of the awake fixating rhesus monkey. Large numbers of these precisely timed spike patterns were found. Information theoretical analysis showed that the precisely timed spike patterns carried only information already available from spike count, suggesting that the number of precisely timed spike patterns was related to firing rate. We therefore examined statistical models relating precisely timed spike patterns to response strength. Previous statistical models use observed properties of neuronal responses such as the peristimulus time histogram, interspike interval, and/or spike count distributions to constrain the parameters of the model. We examined a new stochastic model, which unlike previous models included all three of these constraints and unlike previous models predicted the numbers and types of observed precisely timed spike patterns. This shows that the precise temporal structures of stimulus-elicited responses in LGN and V1 can occur by chance. We show that any deviation of the spike count distribution, no matter how small, from a Poisson distribution necessarily changes the number of precisely timed spike patterns expected in neural responses. Overall the results indicate that the fine temporal structure of responses can only be interpreted once all the coarse temporal statistics of neural responses have been taken into account.
Seizure-Induced Cell Death Produced by Repeated Tetanic Stimulation In Vitro: Possible Role of Endoplasmic Reticulum Calcium Stores
Authors: Pelletier Marc R. , Wadia Jehangir S. , Mills Linda R. , Carlen Peter L.
Published: December 2017

Seizure-induced cell death produced by repeated tetanic stimulation in vitro: possible role of endoplasmic reticulum calcium stores. Seizures may cause brain damage due to mechanisms initiated by excessive excitatory synaptic transmission. One such mechanism is the activation of death-promoting intracellular cascades by the influx and the perturbed homeostasis of Ca2+. The neuroprotective effects of preventing the entry of Ca2+from voltage-dependent Ca2+channels, NMDA receptors, and non-NMDA receptors, is well known. Less clear is the contribution to excitotoxicity of Ca2+released from endoplasmic reticulum (ER) stores. We produced epileptiform discharges in combined entorhinal cortex/hippocampus slices using repeated tetanic stimulation of the Schaffer collaterals and assessed cell death after 1, 3, or 12–14 h with gel electrophoresis of genomic DNA and immunohistologically using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine 5′-triphosphate (dUTP) nick end labeling (TUNEL) staining. We manipulated ER Ca2+stores using two conventional drugs, dantrolene, which blocks the Ca2+release channel, and thapsigargin, which blocks sarco-endoplasmic reticulum Ca2+-ATPases resulting in depletion of ER Ca2+stores. To monitor epileptogenesis, and to assess effects attributable to dantrolene and thapsigargin on normal synaptic transmission, extracellular potentials were recorded in stratum pyramidale of the CA1 region. Repeated tetanic stimulation reliably produced primary afterdischarge and spontaneous epileptiform discharges, which persisted for 14 h, the longest time recorded. We did not observe indications of cell death attributable to seizures with either method when assessed after 1 or 3 h; however, qualitatively more degraded DNA always was observed in tetanized slices from the 12- to 14-h group compared with time-matched controls. Consistent with these data was a significant, fourfold, increase in the percentage of TUNEL-positive cells in CA3, CA1, and entorhinal cortex in tetanized slices from the 12- to 14-h group (16.5 ± 4.4, 33.7 ± 7.1, 11.6 ± 2.1, respectively; means ± SE; n = 7) compared with the appropriate time-matched control (4.1 ± 2.2, 7.3 ± 2.0, 2.8 ± 0.9, respectively; n = 6). Dantrolene (30 μM; n = 5) and thapsigargin (1 μM; n = 4) did not affect significantly normal synaptic transmission, assessed by the amplitude of the population spike after 30 min of exposure. Dantrolene and thapsigargin also were without effect on the induction or the persistence of epileptiform discharges, but both drugs prevented seizure-induced cell death when assessed with gel electrophoresis. We suggest that Ca2+entering a cell from the outside, in addition to the Ca2+contributed from ryanodine-sensitive stores (i.e., Ca2+-induced Ca2+release), may be necessary for seizure-induced cell death.
Cellular Properties of Lateral Spinal Nucleus Neurons in the Rat L6–S1 Spinal Cord
Authors: Jiang M. C. , Liu L. , Gebhart G. F.
Published: December 2017

Cellular properties of lateral spinal nucleus neurons in the rat L6–S1 spinal cord. Conventional intracellular recordings were made from 26 lateral spinal nucleus (LSN) neurons in slices of L6–S1 spinal cord from 10- to 15-day-old rats. At rest, LSN neurons did not fire spontaneous action potentials. With injection of a positive current pulse, action potentials had an amplitude of 72 ± 7 (SD) mV and duration at half-peak height of 0.75 ± 0.22 ms. Action potentials were followed by an afterpotential. Most LSN neurons (13/17) exhibited only an afterhyperpolarization (AHP); four neurons exhibited both a fast and a slow AHP separated by an afterdepolarization (ADP). For LSN neurons that exhibited only an AHP, a slow ADP could be identified during bath application of apamin (100 nM). Four of 11 LSN neurons showed a postinhibitory rebound (PIR). Two types of PIR were noted, one with high threshold and low amplitude and the other with low threshold and high amplitude. The PIR with high amplitude was partially blocked in 0 mM Ca2+/high Mg2+ (10 mM) recording solution. Repetitive firing properties were examined in 17 LSN neurons. On the basis of the ratio of the slopes between initial instantaneous firing and steady-state firing frequencies, neurons with low spike frequency adaptation (SFA, 8/17) and high SFA (4/17) were identified. In addition, 2/17 LSN neurons exhibited biphasic repetitive firing patterns, which were composed of a fast SFA, delayed excitation, and low SFA; another two neurons showed only delayed excitation. Plateau potentials also were found in two LSN neurons. Dorsal root stimulation revealed that most LSN neurons (12/13) had polysynaptic postsynaptic potentials (PSP); only one neuron exhibited a monosynaptic PSP. Electrical stimulation of the dorsal root evoked prolonged discharges in low SFA neurons and a short discharge in high SFA neurons. Intrinsic properties were modulated by bath application of substance P (SP). Membrane potentials were depolarized in all eight LSN neurons tested, and membrane resistance was either increased ( n = 3) or decreased ( n = 2). Both instantaneous firing and steady-state firing were facilitated by SP. In addition, oscillation of membrane potentials were induced in three LSN neurons. These results demonstrate that LSN neurons exhibit a variety of intrinsic properties, which may significantly contribute to sensory processing, including nociceptive processing.
Lack of AMPA Receptor Desensitization During Basal Synaptic Transmission in the Hippocampal Slice
Authors: Hjelmstad Gregory O. , Isaac John T. R. , Nicoll Roger A. , Malenka Robert C.
Published: December 2017

Lack of AMPA receptor desensitization during basal synaptic transmission in the hippocampal slice. Excitatory postsynaptic currents in the CA1 region of rat hippocampal slices are mediated primarily by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in response to synaptically released glutamate. Outside-out patches from pyramidal cells in this region have shown that AMPA receptors are desensitized by short (1 ms) pulses of glutamate. We have taken a number of approaches to ask whether synaptic receptors desensitize in response to synaptically released glutamate in the slice. Recordings with paired pulses and minimal stimulation conditions that are presumably activating only a single release site do not show evidence for desensitization. Furthermore, cyclothiazide, a drug that blocks desensitization, does not alter paired-pulse ratios even under conditions of high probability of release, which should maximize desensitization. These results suggest that synaptic receptors do not desensitize in response to synaptically released glutamate during basal synaptic transmission.
Contribution of the Cerebellar Flocculus to Gaze Control during Active Head Movements
Authors: Belton T. , McCrea R. A.
Published: December 2017

Contribution of the cerebellar flocculus to gaze control during active head movements. The flocculus and ventral paraflocculus are adjacent regions of the cerebellar cortex that are essential for controlling smooth pursuit eye movements and for altering the performance of the vestibulo-ocular reflex (VOR). The question addressed in this study is whether these regions of the cerebellum are more globally involved in controlling gaze, regardless of whether eye or active head movements are used to pursue moving visual targets. Single-unit recordings were obtained from Purkinje (Pk) cells in the floccular region of squirrel monkeys that were trained to fixate and pursue small visual targets. Cell firing rate was recorded during smooth pursuit eye movements, cancellation of the VOR, combined eye-head pursuit, and spontaneous gaze shifts in the absence of targets. Pk cells were found to be much less sensitive to gaze velocity during combined eye–head pursuit than during ocular pursuit. They were not sensitive to gaze or head velocity during gaze saccades. Temporary inactivation of the floccular region by muscimol injection compromised ocular pursuit but had little effect on the ability of monkeys to pursue visual targets with head movements or to cancel the VOR during active head movements. Thus the signals produced by Pk cells in the floccular region are necessary for controlling smooth pursuit eye movements but not for coordinating gaze during active head movements. The results imply that individual functional modules in the cerebellar cortex are less involved in the global organization and coordination of movements than with parametric control of movements produced by a specific part of the body.
GABA-Induced Cl− Current in Cultured Embryonic Human Dorsal Root Ganglion Neurons
Authors: Valeyev Alexander Y. , Hackman John C. , Holohean Alice M. , Wood Patrick M. , Katz Jennifer L. , Davidoff Robert A.
Published: December 2017

γ-Aminobutyric acid (GABA)-activated channels in embryonic (5–8 wk old) human dorsal root ganglion (DRG) neurons in dissociated culture were characterized by whole cell and single-channel techniques. All DRG neurons when held at negative holding membrane potentials displayed inward current to micromolar concentrations of GABA applied by pressure pulses from closely positioned micropipettes. The current was directly proportional to the concentration of GABA (EC50, 111 μM; Hill coefficient, 1.7). DRG neurons also responded to micromolar concentrations of pentobarbital and alphaxalone but not to cis-4-aminocrotonic acid (CACA), glycine, or taurine. Baclofen (100 μM) affected neither the holding currents nor K+ conductance (when patch pipettes were filled with 130 mM KCl) caused by depolarizing pulses. Whole cell GABA-currents were blocked by bicuculline, picrotoxin, and t-butylbicyclophosphorothionate (TBPS; all at 100 μM). The reversal potential of whole cell GABA-currents was close to the theoretical Cl− equilibrium potential, shifting with changes in intracellular Cl− concentration in a manner expected for Cl−-selective channels. The whole cell I-V curve for GABA-induced currents demonstrated slight outward rectification with nearly symmetrical outside and inside Cl− concentrations. Spectral analysis of GABA-induced membrane current fluctuations showed that the kinetic components were best fitted by a triple Lorentzian function. The apparent elementary conductance for GABA-activated Cl− channels determined from the power spectra was 22.6 pS. Single-channel recordings from cell-attached patches with pipettes containing 10 μM GABA indicated that GABA-activated channels have a main and a subconductance level with values of 30 and 19 pS, respectively. Mean open and closed times of the channel were characterized by two or three exponential decay functions, suggesting two or three open channel states and two closed states. Single channels showed a lack of rectification. The actions of GABA on cultured human embryonic DRG neurons are mediated through the activation of GABAA receptors with properties corresponding to those found in the CNS of human and other mammalian species but differing from those of cultured human adult DRG neurons.
Responses of Simultaneously Recorded Respiratory-Related Medullary Neurons to Stimulation of Multiple Sensory Modalities
Authors: Li Zhongzeng , Morris Kendall F. , Baekey David M. , Shannon Roger , Lindsey Bruce G.
Published: December 2017

This study addresses the hypothesis that multiple afferent systems share elements of a distributed brain stem network that modulates the respiratory motor pattern. Data were collected from 18 decerebrate, bilaterally vagotomized, paralyzed, artificially ventilated cats. Up to 28 neurons distributed in the rostral and caudal ventral respiratory group, nucleus tractus solitarius, and raphe obscurus were recorded simultaneously with microelectrode arrays. Phases of the respiratory cycle and inspiratory drive were assessed from integrated efferent phrenic nerve activity. Carotid chemoreceptors were stimulated by injection of CO2-saturated saline solution via the external carotid artery. Baroreceptors were stimulated by increased blood pressure secondary to inflation of an embolectomy catheter in the descending aorta. Cutaneous nociceptors were stimulated by pinching a footpad. Four hundred seventy-four neurons were tested for respiratory modulated firing rates and responses; 403 neurons were tested with stimulation of all 3 modalities. Chemoreceptor stimulation and pinch, perturbations that tend to increase respiratory drive, caused similar responses in 52 neurons; 28 responded oppositely. Chemoreceptor and baroreceptor stimulation resulted in similar primary responses in 45 neurons; 48 responded oppositely. Similar responses to baroreceptor stimulation and pinch were recorded for 38 neurons; opposite effects were measured in 26 neurons. Among simultaneously recorded neurons, distinct combinations of firing rate changes were evoked in response to stimulation of the different modalities. The results show a functional convergence of information from carotid chemoreceptors, baroreceptors, and cutaneous nociceptors on respiratory-modulated neurons distributed in the medulla. The data are consistent with the hypothesis that brain stem neurons have overlapping memberships in multifunctional groups that influence the respiratory motor pattern.
Evidence for Chloride Ions as Intracellular Messenger Substances in Astrocytes
Authors: Bekar Lane K. , Walz Wolfgang
Published: December 2017

Cultured rat hippocampal astrocytes were used to investigate the mechanism underlying the suppression of Ba2+-sensitive K+currents by GABAAreceptor activation. Muscimol application had two effects on whole cell currents: opening of the well-known Cl−channel of the GABAAreceptor and a secondary longer-lasting blockade of outward K+currents displaying both peak and plateau phases. This blockade was independent of both Na+(inside and outside) and ATP in the pipette. It also seemed to be independent of muscimol binding to the receptor because picrotoxin application showed no effect on the K+conductance. The effect is blocked when anion efflux is prevented by replacing Cl−with gluconate (both inside and out) and is enhanced with more permeant anions such as Br−and I−. Moreover, the effect is reproduced in the absence of muscimol by promoting Cl−efflux via lowering of extracellular Cl−levels. These results, along with the requirement for Cl−efflux in muscimol experiments, show a strong dependency of the secondary blockade on Cl−efflux through the Cl−channel of the GABAAreceptor. We therefore conclude that changes in the intracellular Cl−concentration alter the outward K+conductances of astrocytes. Such a Cl−-mediated modulation of an astrocytic K+conductance will have important consequences for the progression of spreading depression through brain tissue and for astrocytic swelling in pathological situations.