bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Common Excitatory and Inhibitory Inputs on Motoneuron Synchronization
Authors: Türker K. S. , Powers R. K.
Published: December 2017

We compared the effects of common excitatory and inhibitory inputs on motoneuron synchronization by simulating synaptic inputs with injected current transients. We elicited repetitive discharge in hypoglossal motoneurons recorded in slices of rat brain stem using a combination of a suprathreshold injected current step with superimposed noise to mimic the synaptic drive likely to occur during physiological activation. The effects of common inputs to motoneurons were simulated by the addition of a waveform composed of from 6 to 300 trains of current transients designed to mimic excitatory and/or inhibitory synaptic currents. We compared the discharge records obtained in several trials in which the same “common input” waveform was applied repeatedly in the presence of different background noise waveforms. The effects of the common input on motoneuron discharge probability and discharge rate were determined by compiling a cross-correlation histogram (CCHist) and a perispike frequencygram (PSFreq) between the discharges of the same cell at different times. Both excitatory and inhibitory common inputs induced synchronous discharge that was evident by a large central peak in the CCHist. The CCHists produced by common excitatory inputs were characterized by larger and narrower central peaks than those generated by common inhibitory inputs. The PSFreqs produced by common excitatory inputs indicated an increase in the discharge rate of motoneurons around time 0 that coincided with the narrow and large central peak in the CCHist. On the other hand, inhibitory inputs often generated very little, if any, change in the discharge rate around time 0 corresponding with the small and wide central peak in the CCHist. These results suggest that the CCHist indicates the effective strength of the net common input but not its sign. Although correlated changes in discharge rate are often quite different for net excitatory and inhibitory common input, except in some restricted conditions, the PSFreq analysis also cannot be used to unambiguously distinguish net excitation from net inhibition.
Cell-Type-Specific GABA Responses and Chloride Homeostasis in the Cortex and Amygdala
Authors: Martina Marzia , Royer Sébastien , Paré Denis
Published: December 2017

The GABA responses of fast-spiking (FS) interneurons and regular-spiking (RS) principal cells were studied using whole cell and perforated-patch recordings in slices of the basolateral amygdala, neo-, and perirhinal cortex. In these three areas, responses to exogenous and synaptically released GABA were abolished by GABAA receptor antagonists in FS cells but also included a GABAB component in RS cells. Moreover, E GABAA of FS and RS cells differed from the calculated E Cl(−61 mV), but in opposite direction (FS, −54 mV; RS, −72 mV). This was not due to a differential dialysis of FS and RS cells by the pipette solution because the discrepancy persisted when recordings were obtained with the perforated-patch-clamp technique, using the cation-selective ionophore gramicidin. Moreover, pharmacological inhibition of cation-chloride cotransporters revealed that the differing E GABAA of FS and RS neurons arises from cell-type-specific chloride homeostatic mechanisms. Indeed, the prevalent regulators of the intracellular chloride concentration are cotransporters that accumulate chloride in FS cells and extrude chloride in RS neurons. Thus, our results suggest that in the basolateral amygdala as well as in the parietal and perirhinal cortices, FS interneurons are more excitable than principal cells not only by virtue of their dissimilar electroresponsive properties but also because they express a different complement of GABA receptors and chloride homeostatic mechanisms.
Direction Tuning of Inhibitory Inputs to the Turtle Accessory Optic System
Authors: Ariel Michael , Kogo Naoki
Published: December 2017

Neurons in turtle accessory optic system (basal optic nucleus, BON) were studied to compare excitatory and inhibitory visual inputs. Using a reduced in vitro brain stem preparation with the eyes attached, previous studies only showed a monosynaptic retinal input to the BON from direction-sensitive retinal ganglion cells that share a common preferred direction. Now using an intact brain stem preparation, not only did BON neurons display inhibitory postsynaptic potentials [IPSP(C)s] spontaneously, but IPSP(C)s were also evoked by visual pattern motion, they had their polarity reversed near the chloride equilibrium potential[Formula: see text] and they were blocked by the GABAA antagonist bicuculline. Because excitatory postsynaptic currents had reversal potentials >0 mV, BON cells were recorded using patch electrodes filled with QX-314 or Cs+ to measure the cell's direction tuning also at that higher reversal potential. For most of the BON neurons studied, their visual excitation and inhibition had a very similar preferred direction, indicating that both synaptic inputs were maximally active onto the same cell under the same stimulus conditions. These competing inputs may result from connections between the pretectum and accessory optic nuclei. Such synaptic interactions may serve a functional role in the visual processing necessary to create retinal slip signals for oculomotor control.
Neuronal Bursting Induced by NK3 Receptor Activation in the Neonatal Rat Spinal Cord In Vitro
Authors: Marchetti Cristina , Nistri Andrea
Published: December 2017

Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period ± SD was 2.8 ± 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5–20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 ± 2 s (average interburst interval 55 ± 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-d-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.
Fine-Scale Organization of SI (Area 3b) in the Squirrel Monkey Revealed With Intrinsic Optical Imaging
Authors: Chen Li Min , Friedman Robert M. , Ramsden Benjamin M. , LaMotte Robert H. , Roe Anna Wang
Published: December 2017

Optical imaging of intrinsic cortical activity was used to study the somatotopic map and the representation of pressure, flutter, and vibration in area 3b of the squirrel monkey ( Saimiri sciureus) cortex under pentothal or isoflurane anesthesia. The representation of the fingerpads in primary somatosensory cortex was investigated by stimulating the glabrous skin of distal fingerpads (D1–D5) with Teflon probes (3-mm diam) attached through an armature to force feedback-controlled torque motors. Under pentothal anesthesia, intrinsic signal maps in area 3b obtained in response to stimulation (trapezoidal indentation) of individual fingerpads showed focal activations. These activations (ranging from 0.5 to 1.0 mm) were discrete and exhibited minimal overlap between adjacent fingerpad representations. Consistent with previously published maps, a somatotopic representation of the fingerpads was observed with an orderly medial to lateral progression from the D5 to D1 fingerpads. Under isoflurane anesthesia, general topography was still maintained, but the representation of fingerpads on adjacent fingers had higher degrees of overlap than with pentothal anesthesia. Multi- and single-unit recordings in the activation zones confirmed the somatotopic maps. To examine preferential inputs from slowly adapting type I (SA) and rapidly adapting type I (RA) and type II (PC) mechanoreceptors, we applied stimuli consisting of sinusoidal indentations that produce sensations of pressure (1 Hz), flutter (30 Hz), and vibration (200 Hz). Under pentothal anesthesia, activation patterns to these different stimuli were focal and coincided on the cortex. Under isoflurane, activation zones from pressure, flutter, and vibratory stimuli differed in size and shape and often contained multiple foci, although overall topography was maintained. Subtraction and vector maps revealed cortical areas (approximate 250-μm diam) that were preferentially activated by the sensations of pressure, flutter, and vibration. Multi- and single-unit recordings aided in the interpretation of the imaging maps. In conclusion, the cortical signals observed with intrinsic signal optical imaging delineated a somatotopic organization of area 3b and revealed different topographical cortical activation patterns for pressure, flutter, and vibratory stimuli. These patterns were dependent on anesthesia type. Possible relationships of these anesthesia effects to somatosensory cortical plasticity are discussed.
Nicotinic Acetylcholine Receptor α7 and α4β2 Subtypes Differentially Control GABAergic Input to CA1 Neurons in Rat Hippocampus
Authors: Alkondon Manickavasagom , Albuquerque Edson X.
Published: December 2017

The hippocampus, a limbic brain region involved in the encoding and retrieval of memory, has a well-defined structural network assembled from excitatory principal neurons and inhibitory interneurons. Because the GABAergic interneurons form synapses onto both pyramidal neurons and interneurons, the activation of nicotinic acetylcholine receptors (nAChRs) present on certain interneurons could induce either inhibition or disinhibition in the hippocampal circuitry. To understand the role of nAChRs in controlling synaptic transmission in the hippocampus, we evaluated the magnitude of nAChR-modulated GABAergic postsynaptic currents (PSCs) in pyramidal neurons and various interneurons of the CA1 region. Using whole cell patch-clamp recording and post hoc identification of neuronal types in rat hippocampal slices, we show that brief (12-s) nAChR activation by ACh (1 mM) or choline (10 mM) enhances the frequency of GABAergic PSCs in both pyramidal neurons and CA1 interneurons. The magnitude of α7 nAChR-mediated GABAergic inhibition, as assessed by the net charge of choline-induced PSCs, was highest in stratum lacunosum moleculare interneurons followed by pyramidal neurons and s. radiatum interneurons. In contrast, the magnitude of α4β2 nAChR-mediated GABAergic inhibition, as assessed by the difference between the net charge of PSCs induced by ACh and choline, was highest in pyramidal neurons followed by s. lacunosum moleculare and s. radiatum interneurons. The present results suggest that cholinergic cues transmitted via specific subtypes of nAChRs modify the synaptic function in the hippocampus by inducing a differential degree of GABAergic inhibition in the target neurons.
Mechanisms Underlying Fictive Feeding inAplysia: Coupling Between a Large Neuron With Plateau Potentials Activity and a Spiking Neuron
Authors: Susswein Abraham J. , Hurwitz Itay , Thorne Richard , Byrne John H. , Baxter Douglas A.
Published: December 2017

The buccal ganglia of Aplysia contain a central pattern generator (CPG) that organizes the rhythmic movements of the radula and buccal mass during feeding. Many of the cellular and synaptic elements of this CPG have been identified and characterized. However, the roles that specific cellular and synaptic properties play in generating patterns of activity are not well understood. To examine these issues, the present study developed computational models of a portion of this CPG and used simulations to investigate processes underlying the initiation of patterned activity. Simulations were done with the SNNAP software package. The simulated network contained two neurons, B31/B32 and B63. The development of the model was guided and constrained by the available current-clamp data that describe the properties of these two protraction-phase interneurons B31/B32 and B63, which are coupled via electrical and chemical synapses. Several configurations of the model were examined. In one configuration, a fast excitatory postsynaptic potential (EPSP) from B63 to B31/B32 was implemented in combination with an endogenous plateau-like potential in B31/B32. In a second configuration, the excitatory synaptic connection from B63 to B31/B32 produced both fast and slow EPSPs in B31/B32 and the plateau-like potential was removed from B31/B32. Simulations indicated that the former configuration (i.e., electrical and fast chemical coupling in combination with a plateau-like potential) gave rise to a circuit that was robust to changes in parameter values and stochastic fluctuations, that closely mimicked empirical observations, and that was extremely sensitive to inputs controlling the onset of a burst. The coupling between the two simulated neurons served to amplify exogenous depolarizations via a positive feedback loop and the subthreshold activation of the plateau-like potential. Once a burst was initiated, the circuit produced the program in an all-or-none fashion. The slow kinetics of the simulated plateau-like potential played important roles in both initiating and maintaining the burst activity. Thus the present study identified cellular and network properties that contribute to the ability of the simulated network to integrate information over an extended period before a decision is made to initiate a burst of activity and suggests that similar mechanisms may operate in the buccal ganglia in initiating feeding movements.
Long-Term Potentiation in the Rat Hippocampus Is Reversibly Depressed by Chronic Intermittent Ethanol Exposure
Authors: Roberto M. , Nelson T. E. , Ur C. L. , Gruol D. L.
Published: December 2017

Alcohol exposure induces multiple neuroadaptive changes in the CNS that can have serious long-term consequences on CNS function including cognitive effects and attenuation of learning and memory. The cellular mechanisms underlying the CNS effects of alcohol have yet to be fully elucidated and are likely to depend on the pattern and dose of alcohol exposure. Using electrophysiological recordings from hippocampal slices obtained from control and chronic alcohol-treated rats, we have investigated the effects of a binge pattern of alcohol abuse on synaptic plasticity in the CNS. The alcohol-treated animals were exposed to ethanol vapor for 12–14 days using an intermittent exposure paradigm (14 h ethanol exposure/10 h ethanol withdrawal daily; blood alcohol levels ∼180 mg/dl), a paradigm that models human binge alcohol use. Induction of long-term potentiation (LTP) in the CA1 region of the hippocampus by tetanic stimulation of Schaffer collaterals was completely blocked in slices from the chronic alcohol-treated animals. LTP remained blocked 1 day after withdrawal of animals from alcohol, indicating that the neuroadaptive changes produced by alcohol were not readily reversible. Partial recovery was observed after withdrawal from alcohol for 5 days. Other measures of synaptic plasticity including posttetanic potentiation and paired-pulse facilitation were also altered by the intermittent alcohol treatment paradigm. The results suggest that alterations in synaptic plasticity induced by chronic intermittent ethanol consumption play an important role in the effects of binge alcohol use on learning and memory function.
Neuronal Activity Patterns in Primate Primary Motor Cortex Related to Trained or Semiautomatic Jaw and Tongue Movements
Authors: Yao Dongyuan , Yamamura Kensuke , Narita Noriyuki , Martin Ruth E. , Murray Gregory M. , Sessle Barry J.
Published: December 2017

The present study was undertaken to determine the firing patterns and the mechanoreceptive field (RF) properties of neurons within the face primary motor cortex (face-MI) in relation to chewing and other orofacial movements in the awake monkey. Of a total of 107 face-MI neurons recorded, 73 of 74 tested had activity related to chewing and 47 of 66 neurons tested showed activity related to a trained tongue task. Of the 73 chewing-related neurons, 52 (71.2%) showed clear rhythmic activity during rhythmic chewing. A total of 32 (43.8%) also showed significant alterations in activity in relation to the swallowing of a solid food (apple) bolus. Many of the chewing-related neurons (81.8% of 55 tested) had an orofacial RF, which for most was on the tongue dorsum. Tongue protrusion was evoked by intracortical microstimulation (ICMS) at most (63.6%) of the recording sites where neurons fired during the rhythmic jaw-opening phase, whereas tongue retraction was evoked by ICMS at most (66.7%) sites at which the neurons firing during the rhythmic jaw-closing phase were recorded. Of the 47 task-related neurons, 21 of 22 (95.5%) examined also showed chewing-related activity and 29 (61.7%) demonstrated significant alteration in activity in relation to the swallowing of a juice reward. There were no significant differences in the peak firing frequency among neuronal activities related to chewing, swallowing, or the task. These findings provide further evidence that face-MI may play an important role not only in trained orofacial movements but also in chewing as well as swallowing, including the control of tongue and jaw movements that occur during the masticatory sequence.
Properties of the Pathways From the Lateral Amygdal Nucleus to Basolateral Nucleus and Amygdalostriatal Transition Area
Authors: Wang Chunsheng , Kang-Park Maeng-Hee , Wilson Wilkie A. , Moore Scott D.
Published: December 2017

Studies have revealed that the amygdala formation is involved in emotional learning, attention, and autonomic functions. Although intra-amygdala connections have been described anatomically, the functional characteristics of these connections are not well understood. We used a rat brain slice preparation with a voltage-sensitive imaging system to compare the electrophysiological characteristics of intra-amygdala pathways. Electrical stimuli delivered to the lateral nucleus (La) caused the optical signal to propagate to basolateral nucleus (BL) and amygdalostriatal transition area (AStr), but not the central nucleus (Ce), consistent with previous anatomical studies, including the recently characterized projections from La to AStr. The velocity of propagation of the evoked potential along the La-AStr pathway was significantly faster than that along the La-BL pathway. In addition, the efficiency of the signal transmission (determined by the rate of decay) along the La-AStr pathway was higher than that along the La-BL pathway. Also, AStr possessed a distinct property of temporal summation of La signals. On the other hand, the La-BL pathway possessed a significantly higher sensitivity to bicuculline/picrotoxin and a stronger paired-pulse inhibition than the La-AStr pathway. Furthermore, the La-BL pathway expressed a higherd-2-amino-5-phosphonovaleric acid (a NMDA blocker) sensitivity than the La-AStr pathway. These results suggest that the La-AStr pathway, which conducts signals with high velocity and less attenuation, may be involved in rapid reflexive responses during fear-induced behavior, whereas the La-BL pathway facilitates signal integration and learning.
Bimodality of Theta Phase Precession in Hippocampal Place Cells in Freely Running Rats
Authors: Yamaguchi Yoko , Aota Yoshito , McNaughton Bruce L. , Lipa Peter
Published: December 2017

The firing of hippocampal principal cells in freely running rats exhibits a progressive phase retardation as the animal passes through a cell's “place” field. This “phase precession” is more complex than a simple linear shift of phase with position. In the present paper, phase precession is quantitatively analyzed by fitting multiple (1–3) normal probability density functions to the phase versus position distribution of spikes in rats making repeated traversals of the place fields. The parameters were estimated by the Expectation Maximization method. Three data sets including CA1 and DG place cells were analyzed. Although the phase-position distributions vary among different cells and regions, this complexity is well described by a superposition of two normal distribution functions, suggesting that the firing behavior consists of two components. This conclusion is supported by the existence of two distinct maxima in the mean spike density in the phase versus position plane. In one component, firing phase shifts over a range of about 180°. The second component, which occurs near the end of the traversal of the place field, exhibits a low correlation between phase and position and is anti-phase with the phase-shift component. The functional implications of the two components are discussed with respect to their possible contribution to learning and memory mechanisms.
LGN Input to Simple Cells and Contrast-Invariant Orientation Tuning: An Analysis
Authors: Troyer Todd W. , Krukowski Anton E. , Miller Kenneth D.
Published: December 2017

We develop a new analysis of the lateral geniculate nucleus (LGN) input to a cortical simple cell, demonstrating that this input is the sum of two terms, a linear term and a nonlinear term. In response to a drifting grating, the linear term represents the temporal modulation of input, and the nonlinear term represents the mean input. The nonlinear term, which grows with stimulus contrast, has been neglected in many previous models of simple cell response. We then analyze two scenarios by which contrast-invariance of orientation tuning may arise. In the first scenario, at larger contrasts, the nonlinear part of the LGN input, in combination with strong push-pull inhibition, counteracts the nonlinear effects of cortical spike threshold, giving the result that orientation tuning scales with contrast. In the second scenario, at low contrasts, the nonlinear component of LGN input is negligible, and noise smooths the nonlinearity of spike threshold so that the input-output function approximates a power-law function. These scenarios can be combined to yield contrast-invariant tuning over the full range of stimulus contrast. The model clarifies the contribution of LGN nonlinearities to the orientation tuning of simple cells and demonstrates how these nonlinearities may impact different models of contrast-invariant tuning.
Propagation of Action Potentials From the Soma to Individual Dendrite of Cultured Rat Amacrine Cells Is Regulated by Local GABA Input
Authors: Yamada Yoshitake , Koizumi Amane , Iwasaki Eisuke , Watanabe Shu-Ichi , Kaneko Akimichi
Published: December 2017

Retinal amacrine cells are interneurons that make lateral and vertical connections in the inner plexiform layer of the retina. Amacrine cells do not possess a long axon, and this morphological feature is the origin of their naming. Their dendrites function as both presynaptic and postsynaptic sites. Half of all amacrine cells are GABAergic inhibitory neurons that mediate lateral inhibition, and their light-evoked response consists of graded voltage changes and regenerative action potentials. There is evidence that the amount of neurotransmitter release from presynaptic sites is increased by spike propagation into the dendrite. Thus understanding of how action potentials propagate in dendrites is important to elucidating the extent and strength of lateral inhibition. In the present study, we used the dual whole cell patch-clamp technique on the soma and the dendrite of cultured rat amacrine cells and directly demonstrated that the action potentials propagate into the dendrites. The action potential in the dendrite was TTX sensitive and was affected by the local membrane potential of the dendrite. Propagation of the action potential was suppressed by local application of GABA to the dendrite. Dual dendrite whole cell patch-clamp recordings showed that GABA suppresses the propagation of action potentials in one dendrite of an amacrine cell, while the action potentials propagate in the other dendrites. It is likely that the action potentials in the dendrites are susceptible to various external factors resulting in the nonuniform propagation of the action potential from the soma of an amacrine cell.
Induction of Active (REM) Sleep and Motor Inhibition by Hypocretin in the Nucleus Pontis Oralis of the Cat
Authors: Xi Ming-Chu , Fung Simon J. , Yamuy Jack , Morales Francisco R. , Chase Michael H.
Published: December 2017

Hypocretin (orexin)-containing neurons in the hypothalamus, which have been implicated in the pathology of narcolepsy, project to nuclei in the brain stem reticular formation that are involved in the control of the behavioral states of sleep and wakefulness. Among these nuclei is the nucleus pontis oralis (NPO). Consequently, the present study was undertaken to determine if the hypocretinergic system provides regulatory input to neurons in the NPO with respect to the generation of the states of sleep and wakefulness. Accordingly, polygraphic recordings and behavioral observations were obtained before and after hypocretin-1 and -2 were microinjected into the NPO in chronic, unanesthetized cats. Microinjections of either hypocretin-1 or -2 elicited, with a short latency, a state of active [rapid eye movement (REM)] sleep that appeared identical to naturally occurring active sleep. The percentage of time spent in active sleep was significantly increased. Dissociated states, which are characterized by the presence of muscle atonia without one or more of the electrophysiological correlates of active sleep, also arose following the injection. The effect of juxtacellular application of hypocretin-1 on the electrical activity of intracellularly recorded NPO neurons was then examined in the anesthetized cat. In this preparation, the application of hypocretin-1 resulted in the depolarization of NPO neurons, an increase in the frequency of their discharge and an increase in their excitability. These latter data represent the first description of the in vivo action of hypocretin on intracellularly recorded neuronal activity and provide evidence that the active sleep-inducing effects of hypocretin are due to a direct excitatory action on NPO neurons. Therefore we suggest that hypocretinergic processes in the NPO may play a role in the generation of active sleep, particularly muscle atonia and therefore are likely to be involved in the pathology of narcolepsy.
Short-Term Dynamics of Synaptic Transmission Within the Excitatory Neuronal Network of Rat Layer 4 Barrel Cortex
Authors: Petersen Carl C. H.
Published: December 2017

The short-term plasticity of synaptic transmission between excitatory neurons within a barrel of layer 4 rat somatosensory neocortex was investigated. Action potentials in presynaptic neurons at frequencies ranging from 1 to 100 Hz evoked depressing postsynaptic excitatory postsynaptic potentials (EPSPs). Recovery from synaptic depression followed an exponential time course with best-fit parameters that differed greatly between individual synaptic connections. The average maximal short-term depression was close to 0.5 with a recovery time constant of around 500 ms. Analysis of each individual sweep showed that there was a correlation between the amplitude of the response to the first and second action potentials such that large first EPSPs were followed by smaller than average second EPSPs and vice versa. Short-term depression between excitatory layer 4 neurons can thus be termed use dependent. A simple model describing use-dependent short-term plasticity was able to closely simulate the experimentally observed dynamic behavior of these synapses for regular spike trains. More complex irregular trains of 10 action potentials occurring within 500 ms were initially well described, but during the train errors increased. Thus for short periods of time the dynamic behavior of these synapses can be predicted accurately. In conjunction with data describing the connectivity, this forms a first step toward computational modeling of the excitatory neuronal network of layer 4 barrel cortex. Simulation of whisking-evoked activity suggests that short-term depression may provide a mechanism for enhancing the detection of objects within the whisker space.
Ca2+/Calmodulin-Dependent Protein Kinase Regulates GABA-Activated Cl−Current in Cockroach Dorsal Unpaired Median Neurons
Authors: Alix Philippe , Grolleau Francoise , Hue Bernard
Published: December 2017

We studied γ-aminobutyric acid (GABA)-mediated currents in short-term cultured dorsal unpaired median (DUM) neurons of cockroach Periplaneta americana using the whole cell patch-clamp technique in symmetrical chloride solutions. All DUM neurons voltage-clamped at −50 mV displayed inward currents ( IGABA) when 10−4M of GABA was applied by pneumatic pressure-ejection pulses. The semi-logarithmic curve of IGABAamplitude versus the ejection time yielded a Hill coefficient of 4.0. IGABAwas chloride (Cl−) because the reversal potential given by the current-voltage ( I-V) curve varied according to the value predicted by the Nernst equation for Cl−dependence. In addition, IGABAwas almost completely blocked by bath application of the chloride channel blockers picrotoxin (PTX) or 3,3-bis(trifluoromethyl)bicyclo-[2,2,1]heptane-2,2-diacarbonitrile (BIDN). The I-V curve for IGABAdisplayed a unexpected biphasic aspect and was best fitted by two linear regressions giving two slope conductances of 35.6 ± 2.1 and 80.9 ± 4.1 nS for potentials ranging from 0 to −30 and −30 to −70 mV, respectively. At −50 mV, the current amplitude was decreased by cadmium chloride (CdCl2, 10−3M) and calcium-free solution. The semi-logarithmic curve for CdCl2-resistant IGABAgave a Hill coefficient of 2.4. Hyperpolarizing voltage step from −50 to −80 mV was known to increase calcium influx through calcium-resting channels. According to this protocol, a significant increase of IGABAamplitude was observed. However, this effect was never obtained when the same protocol was applied on cell body pretreated with CdCl2. When the calmodulin blocker N-(6-aminohexyl)-5-chloro-1-naphtalene-sulfonamide or the calcium-calmodulin-dependent protein kinase blocker 1-[ N,O-bis(5-isoquinolinesulfonyl)- N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62) was added in the pipette solution, IGABAamplitude was decreased. Pressure ejection application of the cis-4-aminocrotonic acid (CACA) on DUM neuron cell body held at −50 mV, evoked a Cl−inward current which was insensitive to CdCl2. The Hill plot yielded a Hill coefficient of 2.3, and the I-V curve was always linear in the negative potential range with a slope conductance of 32.4 ± 1.1 nS. These results, similar to those obtained with GABA in the presence of CdCl2and KN-62, indicated that CACA activated one subtype of GABA receptor. Our study demonstrated that at least two distinct subtypes of Cl−-dependent GABA receptors were expressed in DUM neurons, one of which is regulated by an intracellular Ca2+-dependent mechanism via a calcium-dependent protein kinase. The consequences of the modulatory action of Ca2+in GABA receptors function and their sensitivity to insecticide are discussed.
Electrotonic Coupling in the Inferior Olivary Nucleus Revealed by Simultaneous Double Patch Recordings
Authors: Devor Anna , Yarom Yosef
Published: December 2017

Electrotonic coupling in the inferior olivary (IO) nucleus is assumed to play a crucial role in generating the subthreshold membrane potential oscillations in olivary neurons and in synchronizing climbing fiber input into the cerebellar cortex. We studied the strength and spatial distribution of the coupling by simultaneous double patch recordings from olivary neurons in the brain slice preparation. Electrotonic coupling was observed in 50% of the cell pairs. The coupling coefficient ( CC), defined as the ratio between voltage responses of the post- and the prejunctional cell, varied between 0.002 and 0.17; most of the pairs were weakly coupled. In more than 75% of the pairs, the CCwas <0.05. The coupling resistance varied between 0.7 to 19.8 GΩ, and 68% of the values fell between 0.7 to 8 GΩ. The difference between the coupling coefficient measured on stimulation of cell 1 or cell 2 of a coupled pair was 27 ± 16%. Direct calculation of the coupling resistance revealed an asymmetry of 24 ± 12%, suggesting a directional preference of coupling. The coupling was voltage independent, although depolarization of either the pre- or the postjunctional neuron reduced the CC. The chance of a cell pair being coupled was 80% in immediate neighboring cells, but dropped to about 30% at a distance of 40 μm. No coupled pairs were observed at distances larger than 70 μm. In 52% of staining experiments neurobiotin injection into an olivary neuron produced indirect labeling of 1–11 nearby cells with an average of 3.8 ± 2.9. All indirectly labeled cells were found in, or immediately adjacent, to the dendritic field of the directly stained neuron. Two distinct morphological types of olivary neurons, “curly” and “straight” cells, were found. In each case all neurons stained indirectly by dye passage through gap junctions belonged to the same type. Using the physiological data we estimated that each olivary neuron is directly coupled to about 50 neurons. Since somatic recordings may not reveal coupling through remote dendrites, we conclude that each neuron is directly connected to ≥50 neurons forming two distinct networks of curly and straight cells.
Generation and Propagation of Subthreshold Waves in a Network of Inferior Olivary Neurons
Authors: Devor Anna , Yarom Yosef
Published: December 2017

The cells of the inferior olivary (IO) nucleus generate a large repertoire of electrical signals, among them subthreshold oscillations of the membrane potential (STO). To date, subthreshold oscillations have been studied at the level of single-cell recordings, from which network properties were inferred. In this study we used whole cell patch recordings and optical imaging to address the following issues: 1) synchrony of STO in neighboring neurons; 2) stability of the oscillatory activity in the temporal and spatial domain; and 3) the size of the oscillating network. Recordings were made from 126 pairs of IO neurons in 13- to 30-day-old rats. An additional 262 neurons were recorded individually. The frequency of STO varied from 0.8 to 8.6 Hz. The frequency distribution revealed two subpopulations with peaks at about 3 and 6 Hz. The maximum amplitude among the cells varied from 2 to 25 mV. Oscillations in most neurons showed ongoing modulations in both frequency and amplitude. These modulations were largely abolished following bath application of 40 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive non– N-methyl-d-aspartate (non-NMDA) receptor antagonist, suggesting that they were caused by glutamatergic action. In 35 of 61 recorded pairs at least one neuron exhibited STO permitting us to compare frequency and phase relations. In 22 pairs there was coherent activity with zero phase difference between oscillations in the 2 cells. In these pairs, frequency and amplitude modulation occurred simultaneously in both neurons. Electrotonic coupling was tested in 13 pairs, that had coherent STO, and it was detected in 12. An additional seven pairs showed coherent oscillations but with a phase difference of 20–50 ms. Electrotonic coupling was observed in three of these pairs. Electrotonic coupling was also observed in two of five pairs in which only one neuron oscillated. No coupling was detected in one pair where both neurons oscillated but at different frequencies. Optical imaging using a voltage-sensitive dye (RH 414) was performed on 40 IO slices using an array of 128 photodiodes. Patches of oscillatory activity were observed in 10 slices. Among them six showed spontaneous oscillations, and four exhibited oscillations following extracellular stimulation. In agreement with cell pair recording, optical imaging demonstrated phase-shifted activity in the form of propagating waves of activity within an oscillating patch. We conclude that 1) STO exhibit ongoing modulations of frequency and amplitude that are probably caused by extrinsic inputs to the IO nucleus; 2) electrotonically coupled neurons show a high level of STO synchrony; and 3) the oscillatory activity can propagate within a network of coupled olivary neurons.
Long-Term Deprivation of Substance P in PPT-A Mutant Mice Alters the Anoxic Response of the Isolated Respiratory Network
Authors: Telgkamp Petra , Cao Yuqing Q. , Basbaum Allan I. , Ramirez Jan-Marino
Published: December 2017

The aim of this study was to elucidate the role of the neuromodulator substance P and its related tachykinin neurokinin A (NKA) in the homeostasis of respiratory activity. Respiratory activities, in form of fictive eupneic and sigh activities, were recorded extracellularly from the preBötzinger complex (PBC) in normoxic and anoxic conditions using medullary slice preparations. The effect of a blockade of endogenous substance P was assessed by an acute pharmacological blockade of the receptors with spantide in wild-type animals and by the use of preprotachykinin-A (PPT-A) mutants. These mutants lack from birth the PPT-A gene, which codes for the precursor of substance P and NKA. Spantide treatment reduced frequency (−37%, n = 9) and regularity (twofold) of eupneic-like respiratory activity under normoxic conditions, whereas in PPT-A mutants, eupneic-like activity was under normoxic conditions not significantly different from the wild-type mice (WT). The response to short anoxic episodes (5 min) was characterized in the WT by an increase in respiratory frequencies at the onset of anoxia (ratio anoxic/control frequency = 1.9 ± 0.2, n = 18). This anoxic ratio was unaltered in the presence of spantide (ratio = 2.3 ± 0.4, n = 8) but increased in the mutant (ratio = 4.1, n = 15).

We conclude that endogenously released substance P is important for the maintenance of regular respiratory activity. Short-term blockade of substance P receptors decreases the frequency and regularity of rhythmic activity. Long-term deficiency in substance P leads to compensatory mechanisms that result in an apparently normal respiratory activity under normoxic conditions but a significantly altered response of the respiratory network during anoxia.
Cortical Representation of Venous Nociception in Humans
Authors: Ploner Markus , Holthusen Holger , Noetges Peter , Schnitzler Alfons
Published: December 2017

Painful sensations can be evoked by application of thermal, mechanical, and chemical stimuli to the blood vessels. The cortical substrates of these sensations are unknown. We therefore used whole-head magnetoencephalography to record cortical responses to painful laser stimuli applied cutaneously and intravenously to the dorsum of the hand in healthy human subjects. Similar to the cutaneous stimuli, venous stimulation nearly simultaneously activated the contralateral primary and the bilateral secondary somatosensory cortices. In the venous stimulation condition, all activation peaks were about 50 ms earlier than in the cutaneous stimulation condition. Locations of responses to both stimuli did not differ. These results show that the afferent volley from the veins reaches the cerebral cortex significantly earlier than that from the skin. This might be due to differences in peripheral conduction velocity. Apart from this, these findings demonstrate that venous nociception shares the cortical representation of cutaneous nociception in human somatosensory cortices. Thus the cortical representation of nociceptive processing from tissues of mesodermal and ectodermal origin appears to be similar.
Effect of Volitional Inhibition on Cortical Inhibitory Mechanisms
Authors: Sohn Young H. , Wiltz Katy , Hallett Mark
Published: December 2017

To investigate the effect of volitional inhibition on cortical inhibitory mechanisms, we performed transcranial magnetic stimulation (TMS) studies with a Go/NoGo reaction task in seven healthy subjects. Subjects were asked to extend their right index finger only after Go, but to remain relaxed after NoGo. Single- and paired-pulse TMS were triggered at the average reaction time for the Go response in each subject after Go or NoGo cues. Motor evoked potentials were recorded in the extensor indicis proprius (EIP) and abductor digiti minimi (ADM) muscles of right hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals (ISIs) of 2 ms [short intracortical inhibition (SICI)] and 15 ms [intracortical facilitation (ICF)] and that with suprathreshold conditioning stimuli at ISI of 80 ms [long intracortical inhibition (LICI)] were performed in both Go/NoGo and control conditions. Inhibition of SICI was enhanced in both EIP and ADM after NoGo and was reduced only in EIP after Go. Inhibition of LICI was reduced in both muscles during both conditions, while ICF was not altered. The present results demonstrate that volitional inhibition enhances SICI but reduces LICI nonselectively. These results suggest that these two inhibitory mechanisms act differently during execution and suppression of voluntary movements.
A Model of Spike-Timing Dependent Plasticity: One or Two Coincidence Detectors?
Authors: Karmarkar Uma R. , Buonomano Dean V.
Published: December 2017

In spike-timing dependent plasticity (STDP), synapses exhibit LTD or LTP depending on the order of activity in the presynaptic and postsynaptic cells. LTP occurs when a single presynaptic spike precedes a postsynaptic one (a positive interspike interval, or ISI), while the reverse order of activity (a negative ISI) produces LTD. A fundamental question is whether the “standard model” of plasticity in which moderate increases in Ca2+ influx through the N-methyl-d-aspartate (NMDA) channels induce LTD and large increases induce LTP, can account for the order and interval sensitivity of STDP. To examine this issue we developed a model that captures postsynaptic Ca2+ influx dynamics and the associativity of the NMDA receptors. While this model can generate both LTD and LTP, it predicts that LTD will be observed at both negative and positive ISIs. This is because longer and longer positive ISIs induce monotonically decreasing levels of Ca2+, which eventually fall into the same range that produced LTD at negative ISIs. A second model that incorporated a second coincidence detector in addition to the NMDA receptor generated LTP at positive intervals and LTD only at negative ones. Our findings suggest that a single coincidence detector model based on the standard model of plasticity cannot account for order-specific STDP, and we predict that STDP requires two coincidence detectors.
Paradoxical Anti-Epileptic Effects of a GluR5 Agonist of Kainate Receptors
Authors: Khalilov Ilgam , Hirsch June , Cossart Rosa , Ben-Ari Yehezkel
Published: December 2017

Kainate generates in adult hippocampal neurons a seizure but also a massive excitation of interneurons and a dramatic increase of the inhibitory drive that impinges on principal cells. This “overinhibition” is largely mediated by GluR5-containing kainate receptors that are enriched on interneurons. Here, using the neonatal intact hippocampus in vitro and the triple chamber, we first show that this mechanism is fully operative in neonatal neurons. We then report that application to one hippocampus of ( RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid—a relatively selective agonist of GluR5 containing kainate receptors—depresses the propagation of seizure generated in the opposite hippocampus by a convulsive agent. We conclude that the selective excitation of interneurons by GluR5-containing kainate receptor agonists opens a new therapeutic approach for the epilepsies.
Short- and Long-Term Plasticity of the Perforant Path Synapse in Hippocampal Area CA3
Authors: McMahon David B.T. , Barrionuevo German
Published: December 2017

The direct perforant path (PP) projection to CA3 is a major source of cortical input to the hippocampal region, yet relatively little is known about the basic properties of physiology and plasticity in this pathway. We tested whether PP long-term potentiation (LTP) in CA3 possesses the Hebbian property of associativity; i.e., whether the firing of fibers of different orders can induce PP LTP. We stimulated PP with weak trains of high-frequency stimulation (HFS), which by itself was below the threshold for LTP induction. The identical HFS was effective in inducing LTP when the mossy fiber pathway (MF) was activated simultaneously, thus demonstrating associative plasticity between the two pathways. We also demonstrated associative LTP between PP and recurrent collateral fibers (RC). PP LTP was blocked by the N-methyl-d-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid in both the associative and homosynaptic induction conditions. Neither MF nor RC fiber HFS alone resulted in permanent changes in PP field excitatory postsynaptic potential (fEPSP) amplitude. However, HFS delivered to either MF or RC alone led to transient heterosynaptic depression of the PP fEPSP. Our results support the conceptual framework that regards CA3 as an autoassociative memory network in which efficient retrieval of previously stored activity patterns is mediated by associative plasticity of the PP synapse.