Coherent Firing Research Articles

Timing control in regulatory networks by multisite protein modifications

Computational and experimental studies have yielded quantitative insights into the role for multisite phosphorylation, and other protein modifications, in cell function. This work has emphasized the creation of thresholds and switches for cellular decisions. To date, the dynamics of phosphorylation events have been disregarded yet could be equally relevant for cell function. Here, we discuss theoretical predictions about the kinetic functions of multisite phosphorylation in regulatory networks and how these predictions relate to experimental findings. Using DNA replication as an example, we demonstrate that multisite phosphorylations can support coherent origin firing and robustness against rereplication. We suggest that multisite protein modifications provide a molecular mechanism to robustly time cellular events in the cell cycle, the circadian clock and signal transduction.

Noise as control parameter in networks of excitable media: Role of the network topology

We analyze coupled FitzHugh-Nagumo oscillators on various network topologies, in particular random diluted and scale-free topologies, under the influence of noise. Similarly to globally coupled excitable units, noise acts as control parameter: changing monotonically its strength, the collective dynamical behavior varies from stable equilibrium solutions to coherent firing of a large fraction, and for even stronger noise to incoherent firing leading to chaotic behavior of the excitable elements. For strong noise the system is less sensitive to the network topology. The specific topology enters via the degree of nodes and determines the average number of spikes. Apart from bifurcation regions, it is the ratio of noise intensity to size that determines the dynamical behavior of average values. Specific behavior such as limit cycles may then be realized for strong noise and large systems or for low noise and small systems. Within bifurcation regions, the actual values of noise intensity and system-size matter independently. Here we analyze in more detail phase portraits of small systems. For a given noise intensity and network topology we have studied the regularity of signals as a function of time. We observe the phenomenon of system-size resonance for a whole interval of noise intensities as long as the degree distribution is homogeneous, so that no fine tuning of the noise is needed. Therefore it is plausible that natural systems make actually use of noise when noise is unavoidably present.

Increasing Memory Capacity and Reducing Spurious States in Neural Networks by Introducing Coherent and Collective Firing

It is well known that higher-order Hopfield nets called multispin models can increase memory capacity to some extent by extending the direct product of spin states to more than second order. However, a group of neurons can then respond degenerately to different loaded patterns, resulting in many spurious states due to cross-talk effects. We present an idea to increase the number of attracting basins for patterns while suppressing the associated spurious states, by introducing coherent and collective firing in multispin groups. We numerically implement the method and test the number, stability, and basin size of the attractors thus created. Increasing the size of a group of coherent excitation suppresses spurious states, stabilizes loaded patterns, and dramatically increases the number of pattern attractors.

A Star-Shaped Network Topology Underlying Synchrony in a Biological Neural System

Event Abstract Back to Event A Star-Shaped Network Topology Underlying Synchrony in a Biological Neural System Ron Jortner1, 2*, Ofer Mazor2, Idan Segev1 and Gilles Laurent2 1 Hebrew University, Israel 2 California Institute of Technology, United States Neural activity in many brain systems is characterized by rhythmic, coherent firing across neurons. Such synchronous oscillatory activity, sometimes appearing in the form of field-potential oscillations, is often transient and induced by particular stimuli or behavioral states. Spike synchronization is suggested to play key roles in neural coding – enhancing coincidence detection at target areas, acting as an internal “clock” for time-binning of neuronal signals and binding percepts across independent pathways. Here, we explore the network architecture underlying the emergence of input-induced synchrony in a biological neural system. The antennal lobe (AL) of the locust is an olfactory relay consisting of excitatory and inhibitory neurons, and exhibits robust oscillatory spike synchronization in response to odor input - synchrony which is mediated by inhibitory neurons and is behaviorally relevant for fine odor-discrimination. We used a combination of electrophysiological methods and cross-correlation analysis to study the connectivity between populations of neurons in the AL, and were thus able to extract its connectivity matrix. We find that excitatory and inhibitory AL neurons connect to each other through extremely dense synaptic pathways, whereas no direct connections exist between the excitatory neurons. Exploring network behavior within a theoretical, “in silico” spiking model of excitatory and inhibitory neurons, we were able to identify a particular regime in network-connectivity space leading to strong and reliable spike synchronization. The experimentally characterized connectivity scheme is found to be situated in the heart of this synchronous regime of theoretical connectivity space. This connectivity scheme – a star-shaped neural topology centered around inhibitory neurons – thus forms a neural module specialized in input synchronization; a design which links network architecture and neural coding in the brain. Conference: Bernstein Symposium 2008, Munich, Germany, 8 Oct - 10 Oct, 2008. Presentation Type: Poster Presentation Topic: All Abstracts Citation: Jortner R, Mazor O, Segev I and Laurent G (2008). A Star-Shaped Network Topology Underlying Synchrony in a Biological Neural System. Front. Comput. Neurosci. Conference Abstract: Bernstein Symposium 2008. doi: 10.3389/conf.neuro.10.2008.01.068 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: 17 Nov 2008; Published Online: 17 Nov 2008. * Correspondence: Ron Jortner, Hebrew University, Jerusalem, Israel, ronijort@alice.nc.huji.ac.il 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 Ron Jortner Ofer Mazor Idan Segev Gilles Laurent Google Ron Jortner Ofer Mazor Idan Segev Gilles Laurent Google Scholar Ron Jortner Ofer Mazor Idan Segev Gilles Laurent PubMed Ron Jortner Ofer Mazor Idan Segev Gilles Laurent 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.

Distributed and Associative Working Memory

This study explores the cortical cell dynamics of unimodal and cross-modal working memory (WM). Neuronal activity was recorded from parietal areas of monkeys performing delayed match-to-sample tasks with tactile or visual samples. Tactile memoranda (haptic samples) consisted of rods with differing surface features (texture or orientation of ridges) perceived by active touch. Visual memoranda (icons) consisted of striped patterns of differing orientation. In a haptic-haptic task, the animal had to retain through a period of delay the surface feature of the sample rod to select a rod that matched it. In a visual-haptic task, the animal had to retain the icon for the haptic choice of a rod with ridges of the same orientation as the icon's stripes. Units in all areas responded with firing change to one or more task events. Also in all areas, cells responded differently to different sample memoranda. Differential sample coherent firing was present in most areas during the memory period (delay). It is concluded that neurons in somatosensory and association areas of parietal cortex participate in broad networks that represent various task events and stimuli (auditory, motor, proprioceptive, tactile, and visual). Neurons in the same networks take part in retaining in WM the memorandum for each trial, whether it is encoded haptically or visually. The VH association by parietal cells in WM is analogous to the auditory-visual association previously observed in prefrontal cortex. Both illustrate the capacity of cortical neurons to associate sensory information across time and across modalities in accord with the rules of a behavioral task.

Integration of the sensory inputs to place cells: What, where, why, and how?

The hippocampal place cells are a highly multimodal class of neurons, receiving information from many different sensory sources to correctly localize their firing to restricted regions of an environment. Evidence suggests that the sensory information is processed upstream of the hippocampus, to extract both angular and linear metric information, and also contextual information. These various kinds of information need to be integrated for coherent firing fields to be generated, and the present article reviews recent evidence concerning how this occurs. It is concluded that there is a functional dissociation of the cortical inputs, with one class of incoming information comprising purely metric information concerning distance and orientation, probably routed via the grid cells and head direction cells. The other class of information is much more heterogeneous and serves, at least in part, to contextualize the spatial inputs so as to provide a unique representation of the place the animal is in. Evidence from remapping studies suggests that the metric and contextual inputs interact upstream of the place cells, perhaps in entorhinal cortex. A full understanding of the generation of the hippocampal place representation will require elucidation of the representational functions of the afferent cortical areas.

Spike Timing Amplifies the Effect of Electric Fields on Neurons: Implications for Endogenous Field Effects

Despite compelling phenomenological evidence that small electric fields (<5 mV/mm) can affect brain function, a quantitative and experimentally verified theory is currently lacking. Here we demonstrate a novel mechanism by which the nonlinear properties of single neurons "amplify" the effect of small electric fields: when concurrent to suprathreshold synaptic input, small electric fields can have significant effects on spike timing. For low-frequency fields, our theory predicts a linear dependency of spike timing changes on field strength. For high-frequency fields (relative to the synaptic input), the theory predicts coherent firing, with mean firing phase and coherence each increasing monotonically with field strength. Importantly, in both cases, the effects of fields on spike timing are amplified with decreasing synaptic input slope and increased cell susceptibility (millivolt membrane polarization per field amplitude). We confirmed these predictions experimentally using CA1 hippocampal neurons in vitro exposed to static (direct current) and oscillating (alternating current) uniform electric fields. In addition, we develop a robust method to quantify cell susceptibility using spike timing. Our results provide a precise mechanism for a functional role of endogenous field oscillations (e.g., gamma) in brain function and introduce a framework for considering the effects of environmental fields and design of low-intensity therapeutic neurostimulation technologies.

Clustering behavior in a three-layer system mimicking olivo-cerebellar dynamics

A model is presented that simulates the process of neuronal synchronization, formation of coherent activity clusters and their dynamic reorganization in the olivo-cerebellar system. Three coupled 2D lattices dealing with the main cellular groups in this neuronal circuit are used to model the dynamics of the excitatory feedforward loop linking the inferior olive (IO) neurons to the cerebellar nuclei (CN) via collateral axons that also proceed to terminate as climbing fiber afferents to Purkinje cells (PC). Inhibitory feedback from the CN-lattice fosters decoupling of units in a vicinity of a given IO neuron. It is shown that noise-sustained oscillations in the IO-lattice are capable to synchronize and generate coherent firing clusters in the layer accounting for the excitable collateral axons. The model also provides phase resetting of the oscillations in the IO-lattices with transient silent behavior. It is also shown that the CN–IO feedback leads to transient patterns of couplings in the IO and to a dynamic control of the size of clusters.

Coordination of central odor representations through transient, non-oscillatory synchronization of glomerular output neurons.

At the first stage of processing in the olfactory pathway, the patterns of glomerular activity evoked by different scents are both temporally and spatially dynamic. In the antennal lobe (AL) of some insects, coherent firing of AL projection neurons (PNs) can be phase-locked to network oscillations, and it has been proposed that oscillatory synchronization of PN activity may encode the chemical identity of the olfactory stimulus. It remains unclear, however, how the brain uses this time-constrained mechanism to encode chemical identity when the stimulus itself is unpredictably dynamic. In the olfactory pathway of the moth Manduca sexta,we find that different odorants evoke gamma-band oscillations in the AL and the mushroom body (a higher-order network that receives input from the AL), but oscillations within or between these two processing stages are not temporally coherent. Moreover, the timing of action potential firing in PNs is not phase-locked to oscillations in either the AL or mushroom body, and the correlation between PN synchrony and field oscillations remains low before, during, and after olfactory stimulation. These results demonstrate that olfactory circuits in the moth are specialized to preserve time-varying signals in the insect's olfactory space, and that stimulus dynamics rather than intrinsic oscillations modulate the uniquely coordinated pattern of PN synchronization evoked by each olfactory stimulus. We propose that non-oscillatory synchronization provides an adaptive mechanism by which PN ensembles can encode stimulus identity while concurrently monitoring the unpredictable dynamics in the olfactory signal that typically occur under natural stimulus conditions.

Independent neuronal oscillators of the rat globus pallidus.

In vivo, neurons of the globus pallidus (GP) and subthalamic nucleus (STN) resonate independently around 70 Hz. However, on the loss of dopamine as in Parkinson's disease, there is a switch to a lower frequency of firing with increased bursting and synchronization of activity. In vitro, type A neurons of the GP, identified by the presence of I(h) and rebound depolarizations, fire at frequencies (<or=80 Hz) in response to glutamate pressure ejection, designed to mimic STN input. The profile of this frequency response was unaltered by bath application of the GABA(A) antagonist bicuculline (10 microM), indicating the lack of involvement of a local GABA neuronal network, while cross-correlations of neuronal pairs revealed uncorrelated activity or phase-locked activity with a variable phase delay, consistent with each GP neuron acting as an independent oscillator. This autonomy of firing appears to arise due to the presence of intrinsic voltage- and sodium-dependent subthreshold membrane oscillations. GABA(A) inhibitory postsynaptic potentials are able to disrupt this tonic activity while promoting a rebound depolarization and action potential firing. This rebound is able to reset the phase of the intrinsic oscillation and provides a mechanism for promoting coherent firing activity in ensembles of GP neurons that may ultimately lead to abnormal and pathological disorders of movement.

Transitions between beta and gamma rhythms in neural systems.

We study the coexistence of different rhythms in a local network of one inhibitory and two excitatory nerve cells for a wide range of the excitatory synapse strength and of the slow K+-channel conductance. The dynamic features of spike trains in the presence of noise are discussed. It is found that noise can both cause switching between different states and induce coherent firing events.

Simplified dynamics in a model of noradrenergic modulation of cognitive performance

Neurophysiological work in monkeys has shown that changes in tonic and stimulus-induced activity in the noradrenergic brainstem nucleus locus coeruleus (LC) are tightly correlated with fluctuations in behavioral performance in a visual discrimination task. Simulation work suggests transitions between observed modes of LC activity may be mediated by changes in the level of coherent firing among individual LC neurons. We have simplified this simulation by abstracting the LC to a simple, excitable system in two variables modeled after the FitzHugh–Nagumo relaxation oscillator. This abstracted LC simulates population-level dynamics of the nucleus relevant to its influence on behavior. Coherence within the nucleus was simulated as a single parameter which amplified external input to the abstracted LC while attenuating tonic, uncorrelated activity. Simulated results captured LC dynamics and their relationship with behavior observed in monkeys. Behavior was further simulated over a range of potential LC states not, as yet, directly observed. These results suggest a reverse sigmoidal relationship between false alarm rate and coherence, and a more complex, non-monotonic relationship between response time and coherence.

Zero-lag synchronous dynamics in triplets of interconnected cortical areas

Oscillatory and synchronized activities involving widespread populations of neurons in neocortex are associated with the execution of complex sensorimotor tasks and have been proposed to participate in the ‘binding’ of sensory attributes during perceptual synthesis. How the brain constructs these coherent firing patterns remains largely unknown. Several mechanisms of intracortical synchronization have been considered, in particular mutual inhibition and reciprocal excitation. These mechanisms fail to account for the zero-lag correlations observed among areas located at different levels in the visual hierarchy because the asymmetric laminar organization of ascending and descending connections in this hierarchy would predict systematic inter-areal phase lags. Here we show through detailed computer simulations that, when triplets rather than pairs of reciprocally connected areas in a cortical hierarchy are considered, zero-lag synchronization emerges naturally from their three-way interactions. These simulations were motivated by the observation that most areas in the cat and macaque monkey visual cortex are organized in such triplets. Our results suggest that patterns of anatomical connections in the mammalian neocortex provide a structural basis for the multi-level synchronization of neuronal activity.

Better Risk Management

<h3>Abstract</h3> Cortical neurons show distinct firing patterns across multiple task-epochs characterized by distinct computational aspects. Recent studies suggest that such distinct patterns underly dynamic population code achieving computational flexibility, whereas neurons in some cortical areas often show coherent firing patterns across epochs. To understand how such coherent single-neuron code contribute to dynamic population code, we analyzed neural responses in the perirhinal cortex (PRC) during cue and reward epochs of a two-alternative forced-choice task. We found that the PRC neurons often encoded the opposite choice-directions between those epochs. By using principal component analysis as population-level analysis, we identified neural subspaces associated with each epoch, which reflected coordinated patterns across the neurons. The cue and reward epochs shared neural dimensions where the choice directions were consistently discriminated. Interestingly, those dimensions were supported by dynamically changing contributions of individual neurons. These results indicated heterogeneity of coherent single-neuron responses in their contribution to population code.

Synaptic GABAA Activation Inhibits AMPA-Kainate Receptor–Mediated Bursting in the Newborn (P0–P2) Rat Hippocampus

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of "silent" glutamatergic synapses to conductive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses starts gradually after P2. Further, GABA via its depolarizing action seems to give rise to grossly synchronous yet slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study field potential recordings and gramicidin perforated and whole cell clamp techniques as well as K(+)-selective microelectrodes were used to examine the relative contributions of AMPA and GABA(A) receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. As early as postnatal day (P0-P2), highly coherent spontaneous firing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 +/- 3 s) consisting of 2.9 +/- 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R-mediated postsynaptic currents (PSCs) in simultaneously recorded pyramidal neurons (7.6 +/- 3.0 unitary currents per burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GABA(A)-R-mediated transmission appeared to exert inhibition in the CA3 pyramidal cell population. The GABA(A)-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABA(A)-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABA(A)-R currents was increased after muscimol application from 0.66 +/- 0.16 s(-1) to 1.43 +/- 0.29 s(-1). It was concluded that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0-P2 in rat hippocampus. Concurrently, although GABA(A)-R-mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.

Short-term synaptic plasticity and network behavior.

We develop a minimal time-continuous model for use-dependent synaptic short-term plasticity that can account for both short-term depression and short-term facilitation. It is analyzed in the context of the spike response neuron model. Explicit expressions are derived for the synaptic strength as a function of previous spike arrival times. These results are then used to investigate the behavior of large networks of highly interconnected neurons in the presence of short-term synaptic plasticity. We extend previous results so as to elucidate the existence and stability of limit cycles with coherently firing neurons. After the onset of an external stimulus, we have found complex transient network behavior that manifests itself as a sequence of different modes of coherent firing until a stable limit cycle is reached.

Emergence of spatio-temporal patterns in neuronal activity.

This paper explores if dynamic modulation of coherent firing serves cortical functions. We recorded neuronal activity in the frontal cortex of behaving monkeys and found that temporal coincidences of spikes firing of different neurons can emerge within a fraction of a second in relation to the animal behavior. The temporal patterns of the correlation could not be predicted from the modulations of the neurons firing rate and finally, the patterns of correlation depend on the distance between neurons. These findings call for a revision of prevailing models of neural coding that solely rely on firing rates. The findings suggest that modification of neuronal interactions can serve as a mechanism by which neurons associate rapidly into a functional group in order to perform a specific computational task. Increased correlation between members of the groups, and decreased or negative correlation with others, enhance the ability to dissociate one group from concurrently activated competing groups. Such modulation of neuronal interactions allows each neuron to become a member of several different groups and participate in different computational tasks.

Solitary waves on manifolds of integrate-and-fire neurons

Abstract We investigate lattices of interacting integrate-and-fire neurons. Excitatory short-range interactions lead to coherent firing patterns such as moving stripes on a two-dimensional surface. They have been suggested as possible explanations of hallucinatory phenomena. Other known formations include rotating spirals and expanding concentric rings. We obtain all of them using a novel two-variable description of integrate-and-fire neurons that allows for a continuum formulation of neural fields. Within our model we can formulate a topological constraint that explains why all the moving coherent patterns have a dimension lower by one unit from that of the manifold. In the presence of strong inhomogeneity, neural continuity breaks down, and the field approximation no longer holds. In that case, one obtains incoherent firing patterns driven by the excitatory interactions.

Solitary waves of integrate-and-fire neural fields.

Arrays of interacting identical neurons can develop coherent firing patterns, such as moving stripes that have been suggested as possible explanations of hallucinatory phenomena. Other known formations include rotating spirals and expanding concentric rings. We obtain all of them using a novel two-variable description of integrate-and-fire neurons that allows for a continuum formulation of neural fields. One of these variables distinguishes between the two different states of refractoriness and depolarization and acquires topological meaning when it is turned into a field. Hence, it leads to a topologic characterization of the ensuing solitary waves, or excitons. They are limited to pointlike excitations on a line and linear excitations, including all the examples noted above, on a two-dimensional surface. A moving patch of firing activity is not an allowed solitary wave on our neural surface. Only the presence of strong inhomogeneity that destroys the neural field continuity allows for the appearance of patchy incoherent firing patterns driven by excitatory interactions.

Internal-noise-enhanced signal transduction in neuronal systems

The ability of a neuron to detect and enhance a weak periodic flow of information within an ``internal-noise'' background has been studied through the mechanism of stochastic resonance. Two kinds of nonlinear synaptic input, a coherent firing of spikes from a number of coupled neurons and an irregular firing of spikes from a single neuron, are considered as the internal noise for a neuron. The output signal-to-noise ratio (SNR) is found to be finite. This nonzero SNR is able to account for the relevant experiments where the SNR is nonzero when the external noise is switched to zero.