Precise Spike Timing Research Articles

State space analysis of synchronous spiking in cortical neural networks

Recent proposals that information in cortical neurons may be encoded by precise spike timing have been challenged by the assumption that neurons in vivo can only operate in a noisy fashion, due to large fluctuations in synaptic input activity. Here, we show that despite the background, volleys of precisely synchronized action potentials can stably propagate within a model network of basic integrate-and-fire neurons. The construction of an iterative mapping for the transmission of synchronized spikes between groups of neurons allows for a two-dimensional state space analysis. An attractor, yielding stable spiking precision in the (sub-)millisecond range, governs the synchronization dynamics.

The Role of Spike Timing in the Coding of Stimulus Location in Rat Somatosensory Cortex

Although the timing of single spikes is known to code for time-varying features of a sensory stimulus, it remains unclear whether time is also exploited in the neuronal coding of the spatial structure of the environment, where nontemporal stimulus features are fundamental. This report demonstrates that, in the whisker representation of rat cortex, precise spike timing of single neurons increases the information transmitted about stimulus location by 44%, compared to that transmitted only by the total number of spikes. Crucial to this code is the timing of the first spike after whisker movement. Complex, single neuron spike patterns play a smaller, synergistic role. Timing permits very few spikes to transmit high quantities of information about a behaviorally significant, spatial stimulus.

海馬ＣＡ１野の入力と出力逆伝搬の時間タイミング依存性ＬＴＰ／ＬＴＤ

Spatial distributions of LTP/LTD were investigated in the CA1 area of hippocampal slices by optical imaging method. A pair of electrical pulse stimuli was used to stimulate the schaffer collateral (Stim. A) and the stratum oriens (Stim. B) with various sets of the relative timing (τ). LTP was induced with -10ms<τ<10ms, τ=0ms led to the widest and strongest LTP. On the other hand, τ=±20ms induced LTD. In particular, this LTD at τ=20ms was something that had not been observed by others using cultured hippocampal neurons. The LTD at τ=20ms was blocked by bicuculline (GABA (gamma-aminobutyric acid) receptor antagonist). The importance of precise spike timing in hippocampal CA1 network is discussed in the light of computational neuroscience involving the covariance learning rule.

Chapter 8 Synchronization and assembly formation in the visual cortex

This chapter describes the experimental findings demonstrating that distributed neural populations in the visual cortex process information in a cooperative way. Evidence accumulated that temporal relations among the responses of concurrently activated neurons convey information, which is unavailable from the single-cell responses alone. A large body of data is compatible with the hypothesis that visual objects are represented by assemblies of synchronously firing neurons. The experimental approaches used in the chapter range from the level of multiple single cells to EEG and MEG recordings and from anaesthetized animal preparations to human experiments with active costive tasks. The central claim of the temporal binding hypothesis is that, relations between features in visual space are represented by synchronization of neural responses, but the concept neither specifies what elementary features are used as building blocks for ensemble formation nor how they are encoded. Therefore, the synchronous assembly concept is compatible with the existence of very different levels of receptive fields (RF) complexity along the non-classical, state-dependent, and visual pathways. The temporal binding hypothesis is also compatible with different strategies how elementary pieces of information are encoded. Evidence for the relevance of precise spike timing of single-cell responses for information processing in the visual cortex casts doubts on average firing rate as the dominant code is used in neuronal processing.

Precise spatiotemporal repeating patterns in monkey primary and supplementary motor areas occur at chance levels.

Precise spatiotemporal patterns in neural discharge are a possible mechanism for information encoding in the brain. Previous studies have found that such patterns repeat and appear to relate to key behavioral events. Whether these patterns occur above chance levels remains controversial. To address this question, we have made simultaneous recordings from between two and nine neurons in the primary motor cortex and supplementary motor area of three monkeys while they performed a precision grip task. Out of a total of 67 neurons, 46 were antidromically identified as pyramidal tract neurons. Sections of recordings 60 s long were searched for patterns involving three or more spikes that repeated at least twice. The allowed jitter for pattern repetition was 3 ms, and the pattern length was limited to 192 ms. In all 11 recordings analyzed, large numbers of repeating patterns were found. To assess the expected chance level of patterns, "surrogate" datasets were generated. These had the same moment-by-moment modulation in firing rate as the experimental spike trains, and matched their interspike interval distribution, but did not preserve the precise timing of individual spikes. The number of repeating patterns in 10 randomly generated surrogates was used to form 99% confidence limits on the repeating pattern count expected by chance. There was close agreement between these confidence limits and the number of patterns seen in the experimental data. Analysis of high complexity patterns was carried out in four long recordings (mean duration 23.2 min, mean number of neurons simultaneously recorded 7.5). This analysis logged only patterns composed of a larger number (7-11) of spikes. The number of patterns seen in the surrogate datasets showed a small but significant excess over those seen in the original experimental data; this is discussed in the context of surrogate generation. The occurrence of repeating patterns in the experimental data were strongly associated with particular phases of the precision grip task; however, a similar task dependence was seen for the surrogate data. When a repeating pattern was used as a template to find inexact matches, in which up to half of the component spikes could be missing, similar numbers of matches were found in experimental and surrogate data, and the time of occurrence of such matches showed the same task dependence. We conclude that the existence of precise repeating patterns in our data are not due to cortical mechanisms that favor this form of coding, since as many, if not more, patterns are produced by spike trains constructed only to modulate their firing rate in the same way as the experimental data, and to match the interspike interval histograms. The task dependence of pattern occurrence is explicable as an artifact of the modulation of neural firing rate. The consequences for theories of temporal coding in the cortex are discussed.

Precise spike timing of tactile-evoked cerebellar golgi cell responses: a reflection of combined mossy fiber and parallel fiber activation?

Introduction In recent years a number of papers emerged with tales of ventures in what J.I. Simpson (this Volume) named terra incognita in the cerebellar cortex: the gray zone (granular layer) between input (mossy fibers) and output (Purkinje cells). This gray zone holds feedforward and feedback circuits which pre-process afferent information before it reaches the Purkinje cells. Some of these recent publications specifically focused on the Golgi cell, the primary inhibitory interneuron of the granular layer circuitry (Dieu- donn6 1998a, b; Maex and De Schutter, 1998a, b; Watanabe et al., 1998; Vos et al., 1999a, b). They unequivocally concluded that Golgi cells do more than control the gain of parallel fiber input to Purkinje cells (see also De Schutter et al., Chapter 6, this Volume), which was suggested to be their only function in the classic cerebellar theories of Man (1969), Albus (1971) and Ito (1984). Figure 1 shows a schematic drawing of the anatomical connections of Golgi cells. Golgi cells receive direct excitatory input from mossy fibers (Hfimori and Szent~igothai, 1966). They are also contacted by parallel fibers (Fox et al., 1967), which excite Golgi cells after activation of granule *Corresponding author. Fax: +32-3-8202669; e-mail: erik@bbf.uia.ac.be cells by mossy fibers. In addition, Golgi cells do not contact each other (nor do granule cells) (Palay and Chan-Palay, 1974). Being inhibitory, Golgi cells exert both a feedback (Eccles et al., 1966b) and a feed-forward (Precht and Llin~is, 1969) inhibition of granule cell activity. The classic view of Golgi cells as local controllers of granule cell

Stable propagation of synchronous spiking in cortical neural networks.

The classical view of neural coding has emphasized the importance of information carried by the rate at which neurons discharge action potentials. More recent proposals that information may be carried by precise spike timing have been challenged by the assumption that these neurons operate in a noisy fashion--presumably reflecting fluctuations in synaptic input and, thus, incapable of transmitting signals with millisecond fidelity. Here we show that precisely synchronized action potentials can propagate within a model of cortical network activity that recapitulates many of the features of biological systems. An attractor, yielding a stable spiking precision in the (sub)millisecond range, governs the dynamics of synchronization. Our results indicate that a combinatorial neural code, based on rapid associations of groups of neurons co-ordinating their activity at the single spike level, is possible within a cortical-like network.

Exact digital simulation of time-invariant linear systems with applications to neuronal modeling.

An efficient new method for the exact digital simulation of time-invariant linear systems is presented. Such systems are frequently encountered as models for neuronal systems, or as submodules of such systems. The matrix exponential is used to construct a matrix iteration, which propagates the dynamic state of the system step by step on a regular time grid. A large and general class of dynamic inputs to the system, including trains of delta-pulses, can be incorporated into the exact simulation scheme. An extension of the proposed scheme presents an attractive alternative for the approximate simulation of networks of integrate-and-fire neurons with linear sub-threshold integration and non-linear spike generation. The performance of the proposed method is analyzed in comparison with a number of multi-purpose solvers. In simulations of integrate-and-fire neurons, Exact Integration systematically generates the smallest error with respect to both sub-threshold dynamics and spike timing. For the simulation of systems where precise spike timing is important, this results in a practical advantage in particular at moderate integration step sizes.

Synaptic Control of Spiking in Cerebellar Purkinje Cells: Dynamic Current Clamp Based on Model Conductances

Previous simulations using a realistic model of a cerebellar Purkinje cell suggested that synaptic control of somatic spiking in this cell type is mediated by voltage-gated intrinsic conductances and that inhibitory rather than excitatory synaptic inputs are more influential in controlling spike timing. In this paper, we have tested these predictions physiologically using dynamic current clamping to apply model-derived synaptic conductances to Purkinje cells in vitro. As predicted by the model, this input transformed the in vitro pattern of spiking into a different spike pattern typically observed in vivo. A net inhibitory synaptic current was required to achieve such spiking, indicating the presence of strong intrinsic depolarizing currents. Spike-triggered averaging confirmed that the length of individual intervals between spikes was correlated to the amplitude of the inhibitory conductance but was not influenced by excitatory inputs. Through repeated presentation of identical stimuli, we determined that the output spike rate was very sensitive to the relative balance of excitation and inhibition in the input conductances. In contrast, the accuracy of spike timing was dependent on input amplitude and was independent of spike rate. Thus, information could be encoded in Purkinje cell spiking in a precise spike time code and a rate code at the same time. We conclude that Purkinje cell responses to synaptic input are strongly dependent on active somatic and dendritic properties and that theories of cerebellar function likely need to incorporate single-cell dynamics to a greater degree than is customary.

Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type

In cultures of dissociated rat hippocampal neurons, persistent potentiation and depression of glutamatergic synapses were induced by correlated spiking of presynaptic and postsynaptic neurons. The relative timing between the presynaptic and postsynaptic spiking determined the direction and the extent of synaptic changes. Repetitive postsynaptic spiking within a time window of 20 msec after presynaptic activation resulted in long-term potentiation (LTP), whereas postsynaptic spiking within a window of 20 msec before the repetitive presynaptic activation led to long-term depression (LTD). Significant LTP occurred only at synapses with relatively low initial strength, whereas the extent of LTD did not show obvious dependence on the initial synaptic strength. Both LTP and LTD depended on the activation of NMDA receptors and were absent in cases in which the postsynaptic neurons were GABAergic in nature. Blockade of L-type calcium channels with nimodipine abolished the induction of LTD and reduced the extent of LTP. These results underscore the importance of precise spike timing, synaptic strength, and postsynaptic cell type in the activity-induced modification of central synapses and suggest that Hebb's rule may need to incorporate a quantitative consideration of spike timing that reflects the narrow and asymmetric window for the induction of synaptic modification.

Presynaptic modulation of Lymnaea neurons evoked by computer-generated spike trains.

To investigate the functional organisation and information processing in Lymnaea neuronal networks, artificial spike trains were elicited in one of the main respiratory interneurons (RPeD1) and the modulation of the firing patterns of postsynaptic cells was examined. This was performed by precisely timing the action potential generation of the presynaptic cell using a computer-controlled voltage clamp amplifier (pattern clamp technique). Induced oscillation (0.1-0.4 Hz) in the firing pattern of RPeD1 spread to a large number of postsynaptic cells, as clearly demonstrated by Fourier power spectra. At the same time, no signs of precise (millisecond) spike timing was observed in the cells studied. The results confirm that the neurons used in our experiments process information as pure rate-coders.

Temporal precision of the encoding of motion information by visual interneurons

Background: There is much controversy about the timescale on which neurons process and transmit information. On the one hand, a vast amount of information can be processed by the nervous system if the precise timing of individual spikes on a millisecond timescale is important. On the other hand, neuronal responses to identical stimuli often vary considerably and stochastic response fluctuations can exceed the mean response amplitude. Here, we examined the timescale on which neural responses could be locked to visual motion stimuli.Results: Spikes of motion-sensitive neurons in the visual system of the blowfly are time-locked to visual motion with a precision in the range of several tens of milliseconds. Nevertheless, different motion-sensitive neurons with largely overlapping receptive fields generate a large proportion of spikes almost synchronously. This precision is brought about by stochastic rather than by motion-induced membrane-potential fluctuations elicited by the common peripheral input. The stochastic membrane-potential fluctuations contain more power at frequencies above 30–40 Hz than the motion-induced potential changes. A model of spike generation indicates that such fast membrane-potential changes are a major determinant of the precise timing of spikes.Conclusions: The timing of spikes in neurons of the motion pathway of the blowfly is controlled on a millisecond timescale by fast membrane-potential fluctuations. Despite this precision, spikes do not lock to motion stimuli on this timescale because visual motion does not induce sufficiently rapid changes in the membrane potential.

Calretinin‐like immunoreactivity in mormyrid and gymnarchid electrosensory and electromotor systems

Calretinin-like immunoreactivity was examined in the electrosensory and electromotor systems of the two families of mormyriform electric fish. Mormyrid fish showed the strongest immunoreactivity in the knollenorgan electroreceptor pathway; in the nucleus of the electrosensory lateral line lobe (ELL) and the big cells of the nucleus exterolateralis pars anterior. Mormyromast and ampullary zones of the ELL showed calretinin-like immunoreactivity in the ganglion, granule, and intermediate cell and fiber layers. Mormyromast zones additionally showed labeling of apical dendrites and commissural cells, but the ampullary zone did not. In the electromotor system, two nuclei in the corollary discharge pathway showed labeling: in the paratrigeminal command-associated nucleus and the juxtalobar nucleus. Gymnarchus niloticus (Gymnarchidae) showed strongest calretinin-like immunoreactivity in part of the phase-coding pathway; in S-type electroreceptor afferents. Zones of the ELL not receiving phase-coder input had weak labeling. The electromotor system showed labeling in the lateral relay nucleus and less strongly in the medullary relay nucleus, but none in the pacemaker. The concentration of calcium-binding proteins in mormyrid and gymnarchid time-coding electrosensory pathways is consistent with the hypothesis that they play a role in preserving temporal information across synapses. Cell types that encode temporal characteristics of stimuli in precise spike times have high levels of calcium-binding proteins, but cells that re-code temporal information into presence or magnitude of activity have low levels. Some cell types in the electromotor pathways and early in the time-coding electrosensory pathways do not follow this hypothesis, and therefore preserve temporal information using a mechanism independent of calcium-binding proteins. In particular, electromotor systems may use extensive electrotonic coupling within nuclei to ensure precise timing. J. Comp. Neurol. 387:341–357, 1997. © 1997 Wiley-Liss, Inc.

Calretinin-like immunoreactivity in mormyrid and gymnarchid electrosensory and electromotor systems

Calretinin-like immunoreactivity was examined in the electrosensory and electromotor systems of the two families of mormyriform electric fish. Mormyrid fish showed the strongest immunoreactivity in the knollenorgan electroreceptor pathway; in the nucleus of the electrosensory lateral line lobe (ELL) and the big cells of the nucleus exterolateralis pars anterior. Mormyromast and ampullary zones of the ELL showed calretinin-like immunoreactivity in the ganglion, granule, and intermediate cell and fiber layers. Mormyromast zones additionally showed labeling of apical dendrites and commissural cells, but the ampullary zone did not. In the electromotor system, two nuclei in the corollary discharge pathway showed labeling: in the paratrigeminal command-associated nucleus and the juxtalobar nucleus. Gymnarchus niloticus (Gymnarchidae) showed strongest calretinin-like immunoreactivity in part of the phase-coding pathway; in S-type electroreceptor afferents. Zones of the ELL not receiving phase-coder input had weak labeling. The electromotor system showed labeling in the lateral relay nucleus and less strongly in the medullary relay nucleus, but none in the pacemaker. The concentration of calcium-binding proteins in mormyrid and gymnarchid time-coding electrosensory pathways is consistent with the hypothesis that they play a role in preserving temporal information across synapses. Cell types that encode temporal characteristics of stimuli in precise spike times have high levels of calcium-binding proteins, but cells that re-code temporal information into presence or magnitude of activity have low levels. Some cell types in the electromotor pathways and early in the time-coding electrosensory pathways do not follow this hypothesis, and therefore preserve temporal information using a mechanism independent of calcium-binding proteins. In particular, electromotor systems may use extensive electrotonic coupling within nuclei to ensure precise timing.

Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input.

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials arising from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varying influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potassium conductances. In particular, acetylcholine, which effects learning and memory, reduces the slow alterhyperpolarization, which contributes to spike frequency adaptation. We used whole-cell patch-clamp recordings of pyramidal neurons in neocortical slices and computational simulations to show, first, that when fluctuating inputs were added to a constant current pulse, spike frequency adaptation was reduced as the amplitude of the fluctuations was increased. High-frequency, high-amplitude fluctuating inputs that resembled in vivo conditions exhibited only weak spike frequency adaptation. Second, bath application of carbachol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input but minimally displaced the spike times by < 3 ms, comparable to the spike jitter observed when a visual stimulus is repeated under in vivo conditions. These results suggest that cholinergic modulation may preserve information encoded in precise spike timing, but not in interspike intervals, and that cholinergic mechanisms other than those involving adaptation may contribute significantly to cholinergic modulation of learning and memory.

Noise, neural codes and cortical organization

Cortical circuitry must facilitate information transfer in accordance with a neural code. In this article we examine two candidate neural codes: information is represented in the spike rate of neurons, or information is represented in the precise timing of individual spikes. These codes can be distinguished by examining the physiological basis of the highly irregular interspike intervals typically observed in cerebral cortex. Recent advances in our understanding of cortical microcircuitry suggest that the timing of neuronal spikes conveys little, if any, information. The cortex is likely to propagate a noisy rate code through redundant, patchy interconnections.

Testicular Responses of House Sparrows and White-Crowned Sparrows to Short Daily Photoperiods with Low Intensities of Light

Testicular Responses of House Sparrows and White-Crowned Sparrows to Short Daily Photoperiods with Low Intensities of Light

EFFECTS EVOKED IN AN AXON BY THE ACTIVITY OF A CONTIGUOUS ONE

EFFECTS EVOKED IN AN AXON BY THE ACTIVITY OF A CONTIGUOUS ONE