Single-cell Spike Research Articles

Theta Phase Entrainment of Single-Cell Spiking in Rat Somatosensory Barrel Cortex and Secondary Visual Cortex Is Enhanced during Multisensory Discrimination Behavior.

Phase entrainment of cells by theta oscillations is thought to globally coordinate the activity of cell assemblies across different structures, such as the hippocampus and neocortex. This coordination is likely required for optimal processing of sensory input during recognition and decision-making processes. In quadruple-area ensemble recordings from male rats engaged in a multisensory discrimination task, we investigated phase entrainment of cells by theta oscillations in areas along the corticohippocampal hierarchy: somatosensory barrel cortex (S1BF), secondary visual cortex (V2L), perirhinal cortex (PER), and dorsal hippocampus (dHC). Rats discriminated between two 3D objects presented in tactile-only, visual-only, or both tactile and visual modalities. During task engagement, S1BF, V2L, PER, and dHC LFP signals showed coherent theta-band activity. We found phase entrainment of single-cell spiking activity to locally recorded as well as hippocampal theta activity in S1BF, V2L, PER, and dHC. While phase entrainment of hippocampal spikes to local theta oscillations occurred during sustained epochs of task trials and was nonselective for behavior and modality, somatosensory and visual cortical cells were only phase entrained during stimulus presentation, mainly in their preferred modality (S1BF, tactile; V2L, visual), with subsets of cells selectively phase-entrained during cross-modal stimulus presentation (S1BF: visual; V2L: tactile). This effect could not be explained by modulations of firing rate or theta amplitude. Thus, hippocampal cells are phase entrained during prolonged epochs, while sensory and perirhinal neurons are selectively entrained during sensory stimulus presentation, providing a brief time window for coordination of activity.

Macroscopic dynamics of neural networks with heterogeneous spiking thresholds.

Mean-field theory links the physiological properties of individual neurons to the emergent dynamics of neural population activity. These models provide an essential tool for studying brain function at different scales; however, for their application to neural populations on large scale, they need to account for differences between distinct neuron types. The Izhikevich single neuron model can account for a broad range of different neuron types and spiking patterns, thus rendering it an optimal candidate for a mean-field theoretic treatment of brain dynamics in heterogeneous networks. Here we derive the mean-field equationsfor networks of all-to-all coupled Izhikevich neurons with heterogeneous spiking thresholds. Using methods from bifurcation theory, we examine the conditions under which the mean-field theory accurately predicts the dynamics of the Izhikevich neuron network. To this end, we focus on three important features of the Izhikevich model that are subject here to simplifying assumptions: (i) spike-frequency adaptation, (ii) the spike reset conditions, and (iii) the distribution of single-cell spike thresholds across neurons. Our results indicate that, while the mean-field model is not an exact model of the Izhikevich network dynamics, it faithfully captures its different dynamic regimes and phase transitions. We thus present a mean-field model that can represent different neuron types and spiking dynamics. The model comprises biophysical state variables and parameters, incorporates realistic spike resetting conditions, and accounts for heterogeneity in neural spiking thresholds. These features allow for a broad applicability of the model as well as for a direct comparison to experimental data.

Desynchronization of slow oscillations in the basal ganglia during natural sleep

Slow oscillations of neuronal activity alternating between firing and silence are a hallmark of slow-wave sleep (SWS). These oscillations reflect the default activity present in all mammalian species, and are ubiquitous to anesthesia, brain slice preparations, and neuronal cultures. In all these cases, neuronal firing is highly synchronous within local circuits, suggesting that oscillation-synchronization coupling may be a governing principle of sleep physiology regardless of anatomical connectivity. To investigate whether this principle applies to overall brain organization, we recorded the activity of individual neurons from basal ganglia (BG) structures and the thalamocortical (TC) network over 70 full nights of natural sleep in two vervet monkeys. During SWS, BG neurons manifested slow oscillations (∼0.5 Hz) in firing rate that were as prominent as in the TC network. However, in sharp contrast to any neural substrate explored thus far, the slow oscillations in all BG structures were completely desynchronized between individual neurons. Furthermore, whereas in the TC network single-cell spiking was locked to slow oscillations in the local field potential (LFP), the BG LFP exhibited only weak slow oscillatory activity and failed to entrain nearby cells. We thus show that synchrony is not inherent to slow oscillations, and propose that the BG desynchronization of slow oscillations could stem from its unique anatomy and functional connectivity. Finally, we posit that BG slow-oscillation desynchronization may further the reemergence of slow-oscillation traveling waves from multiple independent origins in the frontal cortex, thus significantly contributing to normal SWS.

Formal models and quantitative measures of multisensory integration: a selective overview.

Multisensory integration (MI) is defined as the neural process by which unisensory signals are combined to form a new product that is significantly different from the responses evoked by the modality-specific component stimuli. In recent years, MI research has seen exponential growth in the number of empirical and theoretical studies. This study presents a selective overview of formal modeling approaches to MI. Emphasis is on models and measures for behavioral paradigms, such as localization, judgment of temporal order or simultaneity, and reaction times, but some concepts for the modeling of single-cell spike rates are treated as well. We identify a number of essential concepts underlying most model classes, such as Bayesian causal inference, probability summation, coactivation, and time window of integration. Quantitative indexes for measuring and comparing the strength of MI across different paradigms are also discussed. Whereas progress over the last years is remarkable, we point out some strengths and weaknesses of the modeling approaches and discuss some obstacles toward a unified theory of MI.

A single-cell spiking model for the origin of grid-cell patterns.

Spatial cognition in mammals is thought to rely on the activity of grid cells in the entorhinal cortex, yet the fundamental principles underlying the origin of grid-cell firing are still debated. Grid-like patterns could emerge via Hebbian learning and neuronal adaptation, but current computational models remained too abstract to allow direct confrontation with experimental data. Here, we propose a single-cell spiking model that generates grid firing fields via spike-rate adaptation and spike-timing dependent plasticity. Through rigorous mathematical analysis applicable in the linear limit, we quantitatively predict the requirements for grid-pattern formation, and we establish a direct link to classical pattern-forming systems of the Turing type. Our study lays the groundwork for biophysically-realistic models of grid-cell activity.

Noisy Juxtacellular Stimulation In Vivo Leads to Reliable Spiking and Reveals High-Frequency Coding in Single Neurons.

Nanostimulation of single identified neurons in vivo can control spike frequency parametrically and, surprisingly, can even bias the animal's behavioral response. Here, we extend this stimulation protocol to time-dependent broadband noise stimulation in sensory and motor cortices of rat. In response to such stimuli, we found increased temporal spike-time reliability. The information transmission properties reveal, both experimentally and theoretically, that the neurons support high-frequency stimulation beyond the inverse membrane time. Generating a stimulus using the neuron's response properties, we could evoke prescribed spike times with high precision. Our work helps to establish a novel method for precise temporal control of single-cell spiking and provides a simplified biophysical description of single-neuron spiking under time-dependent in vivo-like stimulation.

Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels.

L1 (also known as L1CAM) is a trans-membrane glycoprotein mediating neuron-neuron adhesion through homophilic and heterophilic interactions. Although experimental evidence has implicated L1 in axonal outgrowth, fasciculation and pathfinding, its contribution to voltage-gated Na(+) channel function and membrane excitability has remained unknown. Here, we show that firing rate, single cell spiking frequency and Na(+) current density are all reduced in hippocampal excitatory neurons from L1-deficient mice both in culture and in slices owing to an overall reduced membrane expression of Na(+) channels. Remarkably, normal firing activity was restored when L1 was reintroduced into L1-deficient excitatory neurons, indicating that abnormal firing patterns are not related to developmental abnormalities, but are a direct consequence of L1 deletion. Moreover, L1 deficiency leads to impairment of action potential initiation, most likely due to the loss of the interaction of L1 with ankyrin G that produces the delocalization of Na(+) channels at the axonal initial segment. We conclude that L1 contributes to functional expression and localization of Na(+) channels to the neuronal plasma membrane, ensuring correct initiation of action potential and normal firing activity.

What single-cell stimulation has told us about neural coding.

In recent years, single-cell stimulation experiments have resulted in substantial progress towards directly linking single-cell activity to movement and sensation. Recent advances in electrical recording and stimulation techniques have enabled control of single neuron spiking in vivo and have contributed to our understanding of neuronal coding schemesin the brain. Here, we review single neuron stimulation effects in different brain structures and how they vary with artificially inserted spike patterns. We briefly compare single neuron stimulation with other brain stimulation techniques. A key advantage of single neuron stimulation is the precise control of the evoked spiking patterns. Systematically varying spike patterns and measuring evoked movements and sensations enables 'decoding' of the single-cell spike patterns and provides insights into the readout mechanisms of sensory and motor cortical spikes.

Single cell stimulus selectivities in the macaque middle superior temporal sulcus body patch, defined by fMRI

Event Abstract Back to Event Single cell stimulus selectivities in the macaque middle superior temporal sulcus body patch, defined by fMRI Ivo D. Popivanov1*, Jan Jastorff1, Wim Vanduffel1, 2, 3 and Rufin Vogels1 1 KU Leuven, Belgium 2 MGH Martinos Center, United States 3 Harvard Medical School, United States Single-cell and fMRI studies in non-human primates have shown responses to faces and body parts in the inferotemporal cortex. In the present study we recorded single-cell spiking and local field potential (LFP) activity in and surrounding an fMRI-defined body patch to determine the selectivity for animate and inanimate objects. The stimuli were 100 monochrome images, grouped in 10 classes (10 images each): headless monkey and human bodies, 2 sets of control objects (matched for each of the body classes), monkey and human faces, 4-legged mammals, birds, fruits and sculptures (by H. Moore). We defined two main body responsive patches in the superior temporal sulcus (STS) by fMRI. Recordings focused on the posterior one, located at 2-3 mm anterior to the auditory mediatus. Stimuli were shown for 200 ms during a fixation task. Stimulus position was adapted to the receptive field of the neuron. Single neurons in the body patch responded on average significantly stronger to images of bodies (monkey, human, mammal and bird) than to images of other stimulus classes (including faces). Nevertheless, all neurons showed a large difference in responses to different exemplars of the body classes (high within-class selectivity). Cluster analysis of the neural distances between the images based on net spiking responses and high gamma LFP power revealed two main clusters -all bodies (monkeys, humans, mammals, and birds) vs. all other stimuli (mainly faces, objects, fruits). The sculptures were found equally often in both clusters. Lateral to the body patch at the same A/P level, the neurons responded equally strong to bodies and faces, but less to the images of other classes. Cluster analysis based on the responses of those neurons showed 3 main clusters: bodies vs. Faces vs. other inanimate stimuli. In addition, most neurons showed strong selectivity for the orientation of the image. Keywords: Vision, temporal cortex, bodies, Categories, Rhesus Monkey Conference: Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012. Presentation Type: Poster Presentation Topic: Higher Brain Functions in health and disease: cognition and memory Citation: Popivanov ID, Jastorff J, Vanduffel W and Vogels R (2012). Single cell stimulus selectivities in the macaque middle superior temporal sulcus body patch, defined by fMRI. Conference Abstract: Belgian Brain Council. doi: 10.3389/conf.fnhum.2012.210.00095 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Aug 2012; Published Online: 12 Sep 2012. * Correspondence: Mr. Ivo D Popivanov, KU Leuven, Leuven, 3000, Belgium, ivo.popivanov@med.kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ivo D Popivanov Jan Jastorff Wim Vanduffel Rufin Vogels Google Ivo D Popivanov Jan Jastorff Wim Vanduffel Rufin Vogels Google Scholar Ivo D Popivanov Jan Jastorff Wim Vanduffel Rufin Vogels PubMed Ivo D Popivanov Jan Jastorff Wim Vanduffel Rufin Vogels Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Theta and Gamma Power Increases and Alpha/Beta Power Decreases with Memory Load in an Attractor Network Model

Changes in oscillatory brain activity are strongly correlated with performance in cognitive tasks and modulations in specific frequency bands are associated with working memory tasks. Mesoscale network models allow the study of oscillations as an emergent feature of neuronal activity. Here we extend a previously developed attractor network model, shown to faithfully reproduce single-cell activity during retention and memory recall, with synaptic augmentation. This enables the network to function as a multi-item working memory by cyclic reactivation of up to six items. The reactivation happens at theta frequency, consistently with recent experimental findings, with increasing theta power for each additional item loaded in the network's memory. Furthermore, each memory reactivation is associated with gamma oscillations. Thus, single-cell spike trains as well as gamma oscillations in local groups are nested in the theta cycle. The network also exhibits an idling rhythm in the alpha/beta band associated with a noncoding global attractor. Put together, the resulting effect is increasing theta and gamma power and decreasing alpha/beta power with growing working memory load, rendering the network mechanisms involved a plausible explanation for this often reported behavior.

Variability of spike firing during theta-coupled replay of memories in a simulated attractor network

Simulation work has recently shown that attractor networks can reproduce Poisson-like variability of single cell spiking, with coefficient of variation (Cv2) around unity, consistent with cortical data. However, the use of local variability (Lv) measures has revealed area- and layer-specific deviations from Poisson-like firing. In order to test these findings in silico we used a biophysically detailed attractor network model. We show that Lv well above 1, specifically found in superficial cortical layers and prefrontal areas, can indeed be reproduced in such networks and is consistent with periodic replay rather than persistent firing. The memory replay at the theta time scale provides a framework for a multi-item memory storage in the model.This article is part of a Special Issue entitled Neural Coding.

AMPA/Kainate Receptors Drive Rapid Output and Precise Synchrony in Olfactory Bulb Granule Cells

Gamma frequency (30-70 Hz) synchronized oscillatory activity in the olfactory bulb is widely believed to be important for odor detection and discrimination. As in other circuits with "gamma activity," the activity in the bulb is driven by GABAergic interneurons, specifically a class of axonless cells called granule cells. However, bulb granule cells appear to lack some key mechanistic features that promote rapid synchrony in other circuits, including direct electrical interconnections and dominant actions for fast neurotransmitter receptors. At least under "static" stimulus conditions, granule cells are driven by kinetically slow NMDA receptors. Here, I used patch-clamp recordings in rat olfactory bulb slices to better understand mechanisms that shape granule cell activity under "dynamic" stimulus conditions that mimic a natural odor stimulus. During a 4 Hz patterned stimulation of olfactory nerve afferents, activation of single granule cells was primarily controlled by two classes of AMPA/kainate receptor-mediated synaptic inputs derived from output mitral cells. The rapid kinetics of these receptors, together with inactivation of A-type potassium channels, ensured that granule cells had short spike-response times. Studies in cell pairs, moreover, indicated that excitatory inputs could synchronize granule cells on a rapid time scale (2-5 ms), in turn resulting in phase-locked GABA release onto mitral cells. The precision of granule cell synchrony was controlled by the same biophysical mechanisms that promoted rapid single-cell spiking. These studies demonstrate the mechanistic underpinnings that transform a circuit with slow, uncoupled activity under static conditions into a fast, dynamic circuit operating with high precision under physiological conditions.

Receptive-Field Modification in Rat Visual Cortex Induced by Paired Visual Stimulation and Single-Cell Spiking

Experience-dependent plasticity of visual cortical receptive fields (RFs) involves synaptic modifications in the underlying neural circuits, but the site and mechanism of these modifications remain to be elucidated. Using in vivo whole-cell recordings, we show that pairing visual stimulation at a given retinal location with spiking of a single neuron in developing rat visual cortex induces rapid RF modifications. The time course of the response to the visual stimulus at the paired RF location is altered, with an enhancement of the response preceding the spike time and a reduction following the spike. Such bidirectional modification is consistent with spike timing-dependent plasticity. Response modification also occurs at nearby locations, the direction and magnitude of which are correlated with the change at the paired location. In addition, changes at unpaired locations show a negative correlation with the initial strength of the response, which may facilitate rapid modification of the spatial RF profile.

Impaired neurovascular coupling by transhemispheric diaschisis in rat cerebral cortex.

In acute brain disorders, elimination of the excitatory output from an injured brain region reduces activity in connecting brain regions remote from the lesion site (i.e., diaschisis). The authors examined the effect of functional ablation of the left cerebral cortex by cortical spreading depression (CSD) or topical application of tetrodotoxin on single cell spiking activity, baseline CBF, and neurovascular coupling in the right rat sensory cortex. CSD or tetrodotoxin in left cortex reduced the right cortical spontaneous spike rate by 36% and 45%, respectively. Baseline CBF in the right cortex was unaffected by a left-sided CSD, but decreased by 12% for left cortical application of tetrodotoxin. This suggested dissociation between spontaneous spiking activity and basal CBF. Left in-fraorbital nerve stimulation evoked local field potentials in right cerebral cortex that were reduced in amplitude by 19% for left CSD and by 23% for left tetrodotoxin application. The corresponding declines in the evoked CBF responses were 42% for CSD and 23% for tetrodotoxin. Vascular reactivity to adenosine remained unchanged in right cortex. Thus, transhemispheric diaschisis produced a pronounced decrease in the spontaneous spike rate accompanied by no reduction or a small reduction in basal CBF, and an attenuation in amplitudes of evoked synaptic responses and corresponding rises in CBF. The findings suggest that disturbed neurovascular coupling may contribute to the disturbance in brain function in acute transhemispheric diaschisis.

Synchrony levels during evoked seizure-like bursts in mouse neocortical slices.

Slices (n = 45) from the somatosensory cortex of mouse (P8-13) generated spontaneous bursts of activity (0.10 +/- 0.05 Hz) that were recorded extracellularly. Multiunit action potential (AP) activity was integrated and used as an index of population activity. In this experimental model, seizure-like activity (SLA) was evoked with bicuculline (5-10 microM) or N-methyl-d-aspartate (NMDA, 5 microM). SLA was an episode with repetitive bursting at a frequency of 0.50 +/- 0.06 Hz. To evaluate whether SLA was associated with a change in synchrony, we obtained simultaneous intracellular and extracellular recordings (n = 40) and quantified the relationship between individual cells and the surrounding population of neurons. During the SLA there was an increase in population activity and bursting activity was observed in neurons and areas that were previously silent. We defined synchrony as cellular activity that is consistently locked with the population bursts. Signal-averaging techniques were used to determine this component. To quantitatively assess change in synchronous activity at SLA onset, we estimated the entropy of the single cell's spike trains and subdivided this measure into network burst-related information and noise-related entropy. The burst-related information was not significantly altered at the onset of NMDA-evoked SLA and slightly increased when evoked with bicuculline. The signal-to-noise ratio determined from the entropy estimates showed a significant decrease (instead of an expected increase) during SLA. We conclude that the increased population activity during the SLA is attributed to recruitment of neurons rather than to increased synchrony of each of the individual elements.

Activity-induced changes in cerebellar blood flow

Changes in brain cellular activity are accompanied almost invariably by changes in the local cerebral blood flow (CBF). In most functional imaging studies, the increase in local blood flow is assumed to correlate with an increase in the net spike activity of the neurons in the activated region. The question raised in this work is whether the increase in perfusion correlates to spike activity or synaptic transmission, or both. By utilizing measurements of neuronal activity, i.e., single-cell spike activity and synaptic activity of ensembles of neurons (i.e., field potentials), we were able to show that activity-dependent increases in CBF are independent of spiking activity; however, it can be explained by active and passive pre- and postsynaptic mechanisms distinct from spiking. Our work has primarily been focused on the cerebellar cortex where CBF was monitored by laser-Doppler flowmetry and neuronal activity was measured using a glass electrode positioned close to the Purkinje cell.

Activity-dependent receptive field changes in the surround of adult cat visual cortex lesions.

Extracellular single cell spike activity was recorded in the visual cortex of anaesthetized adult cats at identical sites before and 2 days after focal excitotoxic lesions induced by injections of ibotenic acid. In the surround of the lesions (up to 5 mm from the border of the lesion), the average postlesion receptive field (RF) sizes were not different from the prelesion RFs. However, RFs of neurons with increased postlesion excitability were slightly enlarged; such neurons were mainly found close to the anterior border of the lesion (< or = 1 mm). After applying a visual training procedure for 1 h to the postlesion RFs (repetitive, synchronous stimulation of a part of the RF and the neighbouring unresponsive part of the visual field), there was a small (0.4-0.8 degrees ) but significant and specific increase of RF size in about half of the tested neurons. This RF enlargement was similar to that observed with the same training procedure in the visual cortex of normal cats. Thus, small RF changes can be induced by visual stimulation within one hour in normal cells as well as in cells at the border of cortical lesions. Any differences between normal and lesioned animals appear to be related to lesion-induced changes of excitability.

Single neurons are differently involved in stimulus-specific oscillations in cat visual cortex.

Synchronised oscillatory population events (35-80 Hz; 60-300 ms) can be induced in the visual cortex of cats by specific visual stimulation. The oscillatory events are most prominent in local slow wave field potentials (LFP) and multiple unit spikes (MUA). We investigated how and when single cortical neurons are involved in such oscillatory population events. Simultaneous recordings of single cell spikes, LFP and MUA were made with up to seven microelectrodes. Three states of single cell participation in oscillations were distinguished in spike triggered averages of LFP or MUA from the same electrode: (1) Rhythmic states were characterised by the presence of rhythmicity in single cell spike patterns (35-80 Hz). These rhythms were correlated with LFP and MUA oscillations. (2) Lock-in states lacked rhythmic components in single cell spike patterns, while spikes were phase-coupled with LFP or MUA oscillations. (3) During non-participation states LFP or MUA oscillations were present, but single cell spike trains were neither rhythmic nor phase coupled to these oscillations. Stimulus manipulations (from "optimal" to "suboptimal" for the generation of oscillations) often led to systematic transitions between these states (from rhythmic to lock-in to non-participation). Single cell spike coupling was generally associated with negative peaks in LFP oscillations, irrespective of the cortical separation of single cell and population signals (0-6 mm). Our results suggest that oscillatory cortical population activities are not only supported by local and distant neurons with rhythmic spike patterns, but also by those with irregular patterns in which some spikes occur phase-locked to oscillatory events.

Distribution and morphology of functionally identified neurons in the visual cortex of the rat

The distribution and morphology of functionally identified neurons were examined in the visual cortex of Long Evans pigmented rats. The results, based on qualitative and quantitative analysis of single cell spike activity, have shown that neurons in the rat visual cortex have well-defined receptive field properties and are similar to those reported for animals with more highly developed visual systems. Unlike the cat and monkey, the distribution of receptive field types appeared even throughout the visual cortex. Exception was provided by layer IV which, similar to the more ‘visual’ animals, contained the largest percentage of simple cells. Horseradish peroxidase injected into single, physiologically identified neurons allowed for detailed morphological characterization of functional cell types. Of the cells successfully filled with horseradish peroxidase, complex cells were pyramidal in morphology and located in layers II through VI. Simple cells were both pyramidal and non-pyramidal in appearance and were located in layers II + III and IV. Finally, hypercomplex cells were pyramidal in appearance and their perikarya were situated in layers II + III and V.

Single cell spike activity in the olfactory bulb.

Studies of single-cell spike discharges in the olfactory bulb of the rabbit indicate the presence of three classes of neurons as characterized by their discharge patterns. Cells of class I discharge continuously and spontaneously; class II cells discharge intermittently in bursts, in synchrony with the passage of air through the nose. Cells of classes I and II are unmodified during olfactory stimulation. It appears there are many cells in the olfactory bulb whose discharge patterns are unrelated to excitation of the olfactory receptors by odors. Cells of class III respond to appropriate odors; the response of such cells to some odors and not others indicates that odor specificity is a fundamental characteristic of the olfactory system.