Cellular Firing Research Articles

Loose-patch clamp analysis applied to voltage-gated ionic currents following pharmacological ryanodine receptor modulation in murine hippocampal cornu ammonis-1 pyramidal neurons.

The loose-patch clamp technique was first developed and used in native amphibian skeletal muscle (SkM), offering useful features complementing conventional sharp micro-electrode, gap, or conventional patch voltage clamping. It demonstrated the feedback effects of pharmacological modification of ryanodine receptor (RyR)-mediated Ca2+ release on the Na+ channel (Nav1.4) currents, initiating excitation-contraction coupling in native murine SkM. The effects of the further RyR and Ca2+-ATPase (SERCA) antagonists, dantrolene and cyclopiazonic acid (CPA), additionally implicated background tubular-sarcoplasmic Ca2+ domains in these actions. We extend the loose-patch clamp approach to ion current measurements in murine hippocampal brain slice cornu ammonis-1 (CA1) pyramidal neurons. We explored the effects on Na+ currents of pharmacologically manipulating RyR and SERCA-mediated intracellular store Ca2+ release and reuptake. We adopted protocols previously applied to native skeletal muscle. These demonstrated Ca2+-mediated feedback effects on the Na+ channel function. Experiments applying depolarizing 15ms duration loose-patch clamp steps to test voltages ranging from -40 to 120mV positive to the resting membrane potential demonstrated that 0.5mM caffeine decreased inward current amplitudes, agreeing with the previous SkM findings. It also decreased transient but not prolonged outward current amplitudes. However, 2mM caffeine affected neither inward nor transient outward but increased prolonged outward currents, in contrast to its increasing inward currents in SkM. Furthermore, similarly and in contrast to previous SkM findings, both dantrolene (10μM) and CPA (1μM) pre-administration left both inward and outward currents unchanged. Nevertheless, dantrolene pretreatment still abrogated the effects of subsequent 0.5- and 2-mM caffeine challenges on both inward and outward currents. Finally, CPA abrogated the effects of 0.5mM caffeine on both inward and outward currents, but with 2mM caffeine, inward and transient outward currents were unchanged, but sustained outward currents increased. We, thus, extend loose-patch clamping to establish pharmacological properties of murine CA1 pyramidal neurons and their similarities and contrasts with SkM. Here, evoked though not background Ca2+-store release influenced Nav and Kv excitation, consistent with smaller contributions of background store Ca2+ release to resting [Ca2+]. This potential non-canonical mechanism could modulate neuronal membrane excitability or cellular firing rates.

Cladribine treatment improves cortical network functionality in a mouse model of autoimmune encephalomyelitis

BackgroundCladribine is a synthetic purine analogue that interferes with DNA synthesis and repair next to disrupting cellular proliferation in actively dividing lymphocytes. The compound is approved for the treatment of multiple sclerosis (MS). Cladribine can cross the blood–brain barrier, suggesting a potential effect on central nervous system (CNS) resident cells. Here, we explored compartment-specific immunosuppressive as well as potential direct neuroprotective effects of oral cladribine treatment in experimental autoimmune encephalomyelitis (EAE) mice.MethodsIn the current study, we compare immune cell frequencies and phenotypes in the periphery and CNS of EAE mice with distinct grey and white matter lesions (combined active and focal EAE) either orally treated with cladribine or vehicle, using flow cytometry. To evaluate potential direct neuroprotective effects, we assessed the integrity of the primary auditory cortex neuronal network by studying neuronal activity and spontaneous synaptic activity with electrophysiological techniques ex vivo.ResultsOral cladribine treatment significantly attenuated clinical deficits in EAE mice. Ex vivo flow cytometry showed that cladribine administration led to peripheral immune cell depletion in a compartment-specific manner and reduced immune cell infiltration into the CNS. Histological evaluations revealed no significant differences for inflammatory lesion load following cladribine treatment compared to vehicle control. Single cell electrophysiology in acute brain slices was performed and showed an impact of cladribine treatment on intrinsic cellular firing patterns and spontaneous synaptic transmission in neurons of the primary auditory cortex. Here, cladribine administration in vivo partially restored cortical neuronal network function, reducing action potential firing. Both, the effect on immune cells and neuronal activity were transient.ConclusionsOur results indicate that cladribine exerts a neuroprotective effect after crossing the blood–brain barrier independently of its peripheral immunosuppressant action.

Brain-wide electrical dynamics encode individual appetitive social behavior

The architecture whereby activity across many brain regions integrates to encode individual appetitive social behavior remains unknown. Here we measure electrical activity from eight brain regions as mice engage in a social preference assay. We then use machine learning to discover a network that encodes the extent to which individual mice engage another mouse. This network is organized by theta oscillations leading from prelimbic cortex and amygdala that converge on the ventral tegmental area. Network activity is synchronized with cellular firing, and frequency-specific activation of a circuit within this network increases social behavior. Finally, the network generalizes, on a mouse-by-mouse basis, to encode individual differences in social behavior in healthy animals but fails to encode individual behavior in a 'high confidence' genetic model of autism. Thus, our findings reveal the architecture whereby the brain integrates distributed activity across timescales to encode an appetitive brain state underlying individual differences in social behavior.

Adolescent Nicotine Exposure Induces Molecular and Neuronal Features of Depressive Disorder in Adulthood in the Mesolimbic Dopamine System

Introduction/ObjectivesSmoking tobacco is the leading cause of preventable death world‐wide and the main psychoactive component of tobacco, nicotine, is associated with short‐ and long‐term mood‐state alterations. Adolescent nicotine exposure has been shown to induce long‐term depressive and anxiety‐related symptoms in adulthood. Nicotine exposure increases ventral tegmental area (VTA) dopaminergic (DA) inputs to the nucleus accumbens shell (NAcSh), comprising the mesolimbic DA system. Disturbances in the mesolimbic system are well‐established neuropathological correlates of mood disorders, however, the mechanisms by which adolescent nicotine exposure may cause the later development of mood and anxiety disorders is not currently understood. Mood disorders precipitate changes in activation state of intra‐cellular targets, such as glycogen synthase‐3 (GSK3) and extracellular signal‐regulated kinase (ERK). The objectives of the present study are to examine the effects of adolescent nicotine exposure on later adulthood neurobiological phenotypes associated with mood disorders.MethodsAdolescent male Sprague‐Dawley rats were either administered 0.4mg/kg nicotine or saline vehicle injections three times per day for 11 days during a critical period of rodent adolescent neurodevelopment (post‐natal day 35–45). Rats matured into early adulthood (post‐natal day 65) and the VTA and NAc were subjected to protein extraction to examine intracellular molecular protein expression and activation profiles. Separate vehicle and nicotine‐treated groups underwent electrophysiology to record VTA and NAcSh neuronal activity. The VTA and NAcSh DA and medium spiny neuron (MSN) activity was recorded in vehicle and nicotine treated groups using dual‐cell neuronal recordings. Baseline recordings were examined along with recordings following a 0.4mg/kg nicotine injection and a subthreshold dose of 0.1mg/kg.ResultsConsistent with phenotypes observed in human depression, molecular analyses of the NAc revealed significant increases in the phosphorylation states of ERK1/2 (1: p=0.0219, 2: p=0.0151), GSK3 phosphorylation state (1: p=0.0029, 2: p=0.0028), and pGSK3:tGSK3 (site1: p=0.0165, site2: p=0.0291) in nicotine vs. vehicle treated rats. Furthermore, consistent with dysregulated mesolimbic activity states present in mood disorders, preliminary electrophysiological results indicate a larger increase in VTA DA and NAcSh MSN cellular firing frequency and burst rate in the nicotine treated group compared to the control group when subjected to 0.4mg/kg and o.1mg/kg doses of nicotine in adulthood.ConclusionOur results indicate that nicotine exposure in adolescence elicits long‐term changes in neuronal activity and intracellular molecular activation states, consistent with phenotypes observed in clinical mood disorder populations. Together, these findings identify a novel molecular and neuronal mechanism directly in the mesolimbic DA system, underlying the effects of adolescent nicotine exposure on the later development of mood disorders in adulthood.Support or Funding InformationThis work was supported by the Canadian Institutes of Health Research (MOP‐123378).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intrinsic Cellular Properties and Connectivity Density Determine Variable Clustering Patterns in Randomly Connected Inhibitory Neural Networks.

The plethora of inhibitory interneurons in the hippocampus and cortex play a pivotal role in generating rhythmic activity by clustering and synchronizing cell firing. Results of our simulations demonstrate that both the intrinsic cellular properties of neurons and the degree of network connectivity affect the characteristics of clustered dynamics exhibited in randomly connected, heterogeneous inhibitory networks. We quantify intrinsic cellular properties by the neuron's current-frequency relation (IF curve) and Phase Response Curve (PRC), a measure of how perturbations given at various phases of a neurons firing cycle affect subsequent spike timing. We analyze network bursting properties of networks of neurons with Type I or Type II properties in both excitability and PRC profile; Type I PRCs strictly show phase advances and IF curves that exhibit frequencies arbitrarily close to zero at firing threshold while Type II PRCs display both phase advances and delays and IF curves that have a non-zero frequency at threshold. Type II neurons whose properties arise with or without an M-type adaptation current are considered. We analyze network dynamics under different levels of cellular heterogeneity and as intrinsic cellular firing frequency and the time scale of decay of synaptic inhibition are varied. Many of the dynamics exhibited by these networks diverge from the predictions of the interneuron network gamma (ING) mechanism, as well as from results in all-to-all connected networks. Our results show that randomly connected networks of Type I neurons synchronize into a single cluster of active neurons while networks of Type II neurons organize into two mutually exclusive clusters segregated by the cells' intrinsic firing frequencies. Networks of Type II neurons containing the adaptation current behave similarly to networks of either Type I or Type II neurons depending on network parameters; however, the adaptation current creates differences in the cluster dynamics compared to those in networks of Type I or Type II neurons. To understand these results, we compute neuronal PRCs calculated with a perturbation matching the profile of the synaptic current in our networks. Differences in profiles of these PRCs across the different neuron types reveal mechanisms underlying the divergent network dynamics.

Thalamocortical-auditory network alterations following cuprizone-induced demyelination.

BackgroundDemyelination and remyelination are common pathological processes in many neurological disorders, including multiple sclerosis (MS). Clinical evidence suggests extensive involvement of the thalamocortical (TC) system in patients suffering from MS.MethodsUsing murine brain slices of the primary auditory cortex, we investigated the functional consequences of cuprizone-induced de- and remyelination on neuronal activity and auditory TC synaptic transmission in vitro.ResultsOur results revealed an impact of myelin loss and restoration on intrinsic cellular firing patterns, synaptic transmission, and neuronal plasticity in layer 3 and 4 neurons of the auditory TC network. While there was a complex hyper- and depolarizing shift of the resting membrane potential, spontaneous and induced action potential firing was reduced during demyelination and early remyelination. In addition, excitatory postsynaptic potential amplitudes were decreased and induction of LTP was reduced during demyelination.ConclusionsThese data indicate that demyelination-induced impairment of neurons and network activity within the TC system may underlie clinical symptoms observed in demyelinating diseases, corroborating human findings that disease progression is significantly correlated with microstructural tissue damage of the TC system. Further investigation into focal inflammation-induced demyelination models ex vivo and in vivo are needed to understand the functional implication of local and remote lesion formation on TC network activity in MS.

VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons.

The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens-glutamatergic pathway remains unknown. Here, we report that nAcc photoactivation of mesoaccumbens-glutamatergic fibers promotes aversion. Although we found that these mesoaccumbens-glutamate-fibers lack GABA, the aversion evoked by their photoactivation depends on glutamate and GABA receptor signaling, and not on dopamine receptor signaling. We found that mesoaccumbens-glutamatergic-fibers establish multiple asymmetric synapses on single parvalbumin-GABAergic interneurons, and that nAcc photoactivation of these fibers drives AMPA-mediated cellular firing of parvalbumin-GABAergic interneurons. These parvalbumin-GABAergic-interneurons, in turn, inhibit nAcc medium spiny output neurons, as such, controlling inhibitory neurotransmission within nAcc. The mesoaccumbens-glutamatergic pathway is the first glutamatergic input to nAcc shown to mediate aversion, instead of reward, and the first pathway shown to establish excitatory synapses on nAcc parvalbumin-GABAergic interneurons.

High-frequency stimulation of the medial prefrontal cortex decreases cellular firing in the dorsal raphe.

High-frequency deep brain stimulation (HFS-DBS) of the subcallosal cingulate (SCC) region has been investigated as a treatment for refractory forms of depression with a ~50% remission rate in open label studies. However, the therapeutic mechanisms of DBS are still largely unknown. Using anaesthetized Sprague Dawley rats, we recorded neuronal spiking activity in 102 neurons of the dorsal raphe (DR) before, during and after the induction of a 5-min HFS train in the infralimbic region (IL) of the medial prefrontal cortex (mPFC), the rodent homologue of the human SCC. The majority of DR cells (82%) significantly decreased firing rate during HFS (P<0.01, 55.7±4.5% of baseline, 35 rats). To assess whether mPFC-HFS mediates inhibition of DR cellular firing by stimulating local GABAergic interneurons, the GABAA antagonist bicuculline (Bic, 100μm) was injected directly into the DR during HFS. Neurons inhibited by HFS recovered their firing rate during Bic+HFS (P<0.01, n=15, seven rats) to levels not different from baseline. Cells that were not affected by HFS did not change firing rate during Bic+HFS (P=0.968, n=7, three rats). These results indicate that blocking GABAA reverses HFS-mediated inhibition of DR neurons. As the cells that were not inhibited by HFS were also unaffected by HFS+Bic, they are probably not innervated by local GABA. Taken together, our results suggest that mPFC-HFS may exert a preferential effect on DR neurons with GABAA receptors.

Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents Ih and ISK.

Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. Renshaw cells can be identified in vitro using anatomical and cellular criteria; however, their functional role in locomotion remains poorly defined because of the difficulty of functionally isolating Renshaw cells from surrounding motor circuits. Here we aimed to investigate whether the cholinergic nicotinic receptor alpha2 (Chrna2) can be used to identify Renshaw cells (RCs(α2)) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RCs(α2) properties confirmed that neurons genetically marked by the Chrna2-Cre mouse line together with a fluorescent reporter mouse line are Renshaw cells. Whole-cell patch-clamp recordings revealed that RCs(α2) constitute an electrophysiologically stereotyped population with a resting membrane potential of -50.5 ± 0.4 mV and an input resistance of 233.1 ± 11 MΩ. We identified a ZD7288-sensitive hyperpolarization-activated cation current (Ih) in all RCs(α2), contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RCs(α2) to express small calcium-activated potassium currents (I(SK)) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RCs(α2) can be genetically targeted through their selective Chrna2 expression and that they display currents known to modulate rebound excitation and firing frequency. The genetic identification of Renshaw cells and their electrophysiological profile is required for genetic and pharmacological manipulation as well as computational simulations with the aim to understand their functional role.

An isomorphic mapping hypothesis of the grid representation

We introduce a grid cell microcircuit hypothesis. We propose the ‘grid in the world’ (evident in grid cell discharges) is generated by a ‘grid in the cortex’. This cortical grid is formed by patches of calbindin-positive pyramidal neurons in layer 2 of medial entorhinal cortex (MEC). Our isomorphic mapping hypothesis assumes three types of isomorphism: (i) metric correspondence of neural space (the two-dimensional cortical sheet) and the external two-dimensional space within patches; (ii) isomorphism between cellular connectivity matrix and firing field; (iii) isomorphism between single cell and population activity. Each patch is a grid cell lattice arranged in a two-dimensional map of space with a neural : external scale of approximately 1 : 2000 in the dorsal part of rat MEC. The lattice behaves like an excitable medium with neighbouring grid cells exciting each other. Spatial scale is implemented as an intrinsic scaling factor for neural propagation speed. This factor varies along the dorsoventral cortical axis. A connectivity scheme of the grid system is described. Head direction input specifies the direction of activity propagation. We extend the theory to neurons between grid patches and predict a rare discharge pattern (inverted grid cells) and the relative location and proportion of grid cells and spatial band cells.

Selection of preconfigured cell assemblies for representation of novel spatial experiences

Internal representations about the external world can be driven by the external stimuli or can be internally generated in their absence. It has been a matter of debate whether novel stimuli from the external world are instructive over the brain network to create de novo representations or, alternatively, are selecting from existing pre-representations hosted in preconfigured brain networks. The hippocampus is a brain area necessary for normal internally generated spatial-temporal representations and its dysfunctions have resulted in anterograde amnesia, impaired imagining of new experiences, and hallucinations. The compressed temporal sequence of place cell activity in the rodent hippocampus serves as an animal model of internal representation of the external space. Based on our recent results on the phenomenon of novel place cell sequence preplay, we submit that the place cell sequence of a novel spatial experience is determined, in part, by a selection of a set of cellular firing sequences from a repertoire of existing temporal firing sequences in the hippocampal network. Conceptually, this indicates that novel stimuli from the external world select from their pre-representations rather than create de novo our internal representations of the world.

Distinct preplay of multiple novel spatial experiences in the rat

The activity of ensembles of hippocampal place cells represents a hallmark of an animal's spatial experience. The neuronal mechanisms that enable the rapid expression of novel place cell sequences are not entirely understood. Here we report that during sleep or rest, distinct sets of hippocampal temporal sequences in the rat preplay multiple corresponding novel spatial experiences with high specificity. These findings suggest that the place cell sequence of a novel spatial experience is determined, in part, by an online selection of a subset of cellular firing sequences from a larger repertoire of preexisting temporal firing sequences in the hippocampal cellular assembly network that become rapidly bound to the novel experience. We estimate that for the given context, the recorded hippocampal network activity has the capacity to preplay an extended repertoire of at least 15 future spatial experiences of similar distinctiveness and complexity.

Impact of gamma-oscillatory inhibition on the signal transmission of a cortical pyramidal neuron

Networks of synchronized fast-spiking interneurons are thought to be key elements in the generation of gamma (γ) oscillations (30-80Hz) in the brain. We examined how such γ-oscillatory inhibition regulates the output of a cortical pyramidal cell. Specifically, we modeled a situation where a pyramidal cell receives inputs from γ-synchronized fast-spiking inhibitory interneurons. This model successfully reproduced several important aspects of a recent experimental result regarding the γ-inhibitory regulation of pyramidal cellular firing that is presumably associated with the sensation of whisker stimuli. Through an in-depth analysis of this model system, we show that there is an obvious rhythmic gating effect of the γ-oscillated interneuron networks on the pyramidal neuron's signal transmission. This effect is further illustrated by the interactions of this interneuron network and the pyramidal neuron. Prominent power in the γ frequency range can emerge provided that there are appropriate delays on the excitatory connections and inhibitory synaptic conductance between interneurons. These results indicate that interactions between excitation and inhibition are critical for the modulation of coherence and oscillation frequency of network activities.

Reflections

Reflections

Electric field modulation of theta and gamma rhythms: probe into network connectivity

Introduction and background Subthreshold electric fields are effective in suppressing epilepsy [1], modulating the state of single neurons via polarization [2], and affecting neuronal synchronization [3]. Here we employ detailed computational modeling to test the use of global and local electric fields as a tool for dissecting neural population dynamics and connectivity. For example, modulation of cellular firing by theta rhythms plays an important role in hippocampal cognitive functions. It has been proposed that theta modulation can synchronize cell assemblies across the hippocampus; that place cell firing phase can code for the animal position; and that different phases of theta correlate with learning vs. recall. To demonstrate control of theta and gamma rhythms by electric field (EF), we developed a simplified 2-dimensional CA1 network based on [4] showing theta-modulated high frequency activity of pyramidal neurons [5]. Application of EF alone was able to shift the firing mode of the simplified network in the theta-gamma range.

Episodic activity in a heterogeneous excitatory network, from spiking neurons to mean field

Many developing neural systems exhibit spontaneous activity (O'Donovan, Curr Opin Neurobiol 9:94-104, 1999; Feller, Neuron 22:653-656, 1999) characterized by episodes of discharge (active phases) when many cells are firing, separated by silent phases during which few cells fire. Various models exhibit features of episodic behavior by means of recurrent excitation for supporting an episode and slow activity-dependent depression for terminating one. The basic mechanism has been analyzed using mean-field, firing-rate models. Firing-rate models are typically formulated ad hoc, not derived from a spiking network description, and the effects of substantial heterogeneity amongst the units are not usually considered. Here we develop an excitatory network of spiking neurons (N-cell model) with slow synaptic depression to model episodic rhythmogenesis. This N-cell model displays episodic behavior over a range of heterogeneity in bias currents. Important features of the episodic behavior include orderly recruitment of individual cells during silent phases and existence of a dynamical process whereby a small critical subpopulation of intermediate excitability conveys synaptic drive from active to silent cells. We also derive a general self-consistency equation for synaptic drive that includes cell heterogeneity explicitly. We use this mean-field description to expose the dynamical bistability that underlies episodic behavior in the heterogeneous network. In a systematic numerical study we find that the robustness of the episodic behavior improves with increasing heterogeneity. Furthermore, the heterogeneity of depression variables (imparted by the heterogeneity in cellular firing thresholds) plays an important role in this improvement: it renders the network episodic behavior more robust to variations in excitability than if depression is uniformized. We also investigate the effects of noise vs. heterogeneity on the robustness of episodic behavior, especially important for the developing nervous system. We demonstrate that noise-induced episodes are very fragile, whereas heterogeneity-produced episodic rhythm is robust.

Intrathecal Opioids for Control of Chronic Low Back Pain During Deep Brain Stimulation Procedures

Patients with chronic low back pain may not be able to endure the supine position required by the lengthy deep brain stimulation procedure. Many neurophysiologists severely restrict the use of opioids and sedative drugs during deep brain stimulation procedures due to the concern for depression of cellular firing frequencies used to map the brain for placement of the stimulator leads. We present two cases in which spinal opioids were used to achieve prolonged pain relief in patients with chronic back pain, without altering cellular firing critical for brain mapping.

Variability in neuronal activity in primate cortex during working memory tasks

Persistent elevated neuronal activity has been identified as the neuronal correlate of working memory. It is generally assumed in the literature and in computational and theoretical models of working memory that memory-cell activity is stable and replicable; however, this assumption may be an artifact of the averaging of data collected across trials, and needs experimental verification. In this study, we introduce a classification scheme to characterize the firing frequency trends of cells recorded from the cortex of monkeys during performance of working memory tasks. We examine the frequency statistics and variability of firing during baseline and memory periods. We also study the behavior of cells on individual trials and across trials, and explore the stability of cellular firing during the memory period. We find that cells from different firing-trend classes possess markedly different statistics. We also find that individual cells show substantial variability in their firing behavior across trials, and that firing frequency also varies markedly over the course of a single trial. Finally, the average frequency distribution is wider, the magnitude of the frequency increases from baseline to memory smaller, and the magnitude of frequency decreases larger than is generally assumed. These results may serve as a guide in the evaluation of current theories of the cortical mechanisms of working memory.

Effect of Interictal Spikes on Single‐Cell Firing Patterns in the Hippocampus

The interictal EEG spike(s) is the hallmark of the epileptic EEG. While focal interictal spike (IS) have been associated with transitory cognitive impairment, with the type of deficit dependent on where in the cortex the IS arises, the mechanism by which IS result in transitory dysfunction is not known. The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures. We studied IS in two seizure models; pilocarpine-induced status epilepticus and recurrent flurothyl models. The effect of spontaneous hippocampal spikes on action potentials (APs) of CA1 cells in rats walking in a familiar environment was investigated using 32 extracellular electrodes. We also compared the effect of spikes on two types of hippcampal cells; place cells that discharge rapidly only when the rat's head is in a specific part of the environment, the so-called firing field, and interneurons, which are a main source of inhibition in the hippocampus. IS were associated with a decreased likelihood of AP compared with IS-free portions of the record. Compared to pre-IS baseline, IS were followed by significant decreases in CA1 APs for periods up to 2 s following the IS in both models. When occurring in flurries, IS were associated with a pronounced decrease in APs. The response to IS was cell-dependent; IS resulted in decreases in AP firing after the IS in interneurons but not place cells. This study demonstrates that IS have substantial effects on cellular firing in the hippocampus and that these effects last far longer than the spike and slow wave. Furthermore, the effect of IS on cellular firing was cell specific, affecting interneurons more than place cells. These findings suggest that IS may contribute to seizure-induced cognitive impairment by altering AP firing in a cell-specific manner.

Dynamics of striate cortical activity in the alert macaque: II. Fast time scale synchronization.

Synchronous neuronal activity with millisecond precision has been postulated to contribute to the process of visual perceptual grouping. We have performed multineuron recordings in striate cortex of two alert macaque monkeys to determine if the occurrence and properties of this form of activity are consistent with the minimal requirements of this theory. We find that neuronal synchronization with millisecond precision is a prevalent and robust feature of stimulus-evoked activity in striate cortex. It occurs among adjacent cells recorded by the same electrode (<120 microm), among cells recorded at separate but nearby sites (300-400 microm) and between cells recorded at locations separated by 3-4 mm. The magnitude and probability of synchronous firing is inversely related to the spatial separation between the cells and it occurs within and between groups of cells that are both tuned and untuned for stimulus orientation and direction. Among those tuned for orientation, cell pairs separated by <400 microm showed no clear dependence of correlated firing on orientation preference. The occurrence of gamma-band (20-70 Hz) oscillations in the cellular firing patterns was a strong predictor of synchronous firing at each of the spatial scales. Nearly 90% of the cell pairs showing significant correlation also showed oscillatory firing in one or both cells of the pair. These results are consistent with some, but not all, of the previous reports of synchronous activity in striate cortex of both cat and primates. The similarities in the properties of synchronous oscillations in the monkey and cat suggest that this form of neuronal activity is a general property of mammalian striate cortex. The relation between correlation and oscillation suggests that neuronal rhythmicity is an important mechanism contributing to synchronization.