Synchronous Firing Of Neurons Research Articles

Stochastic Synchrony of Chaos in a Pulse-Coupled Neural Network with Both Chemical and Electrical Synapses Among Inhibitory Neurons

The synchronous firing of neurons in a pulse-coupled neural network composed of excitatory and inhibitory neurons is analyzed. The neurons are connected by both chemical synapses and electrical synapses among the inhibitory neurons. When electrical synapses are introduced, periodically synchronized firing as well as chaotically synchronized firing is widely observed. Moreover, we find stochastic synchrony where the ensemble-averaged dynamics shows synchronization in the network but each neuron has a low firing rate and the firing of the neurons seems to be stochastic. Stochastic synchrony of chaos corresponding to a chaotic attractor is also found.

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures

BackgroundExcitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg2+-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.ResultsWithin 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic reduction in the ability of CA3 to generate firing; and (ii) a contrasting increase in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.ConclusionThese results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.

Functional organization of the basal ganglia: Therapeutic implications for Parkinson's disease

The basal ganglia (BG) are a highly organized network, where different parts are activated for specific functions and circumstances. The BG are involved in movement control, as well as associative learning, planning, working memory, and emotion. We concentrate on the "motor circuit" because it is the best understood anatomically and physiologically, and because Parkinson's disease is mainly thought to be a movement disorder. Normal function of the BG requires fine tuning of neuronal excitability within each nucleus to determine the exact degree of movement facilitation or inhibition at any given moment. This is mediated by the complex organization of the striatum, where the excitability of medium spiny neurons is controlled by several pre- and postsynaptic mechanisms as well as interneuron activity, and secured by several recurrent or internal BG circuits. The motor circuit of the BG has two entry points, the striatum and the subthalamic nucleus (STN), and an output, the globus pallidus pars interna (GPi), which connects to the cortex via the motor thalamus. Neuronal afferents coding for a given movement or task project to the BG by two different systems: (1) Direct disynaptic projections to the GPi via the striatum and STN. (2) Indirect trisynaptic projections to the GPi via the globus pallidus pars externa (GPe). Corticostriatal afferents primarily act to inhibit medium spiny neurons in the "indirect circuit" and facilitate neurons in the "direct circuit." The GPe is in a pivotal position to regulate the motor output of the BG. Dopamine finely tunes striatal input as well as neuronal striatal activity, and modulates GPe, GPi, and STN activity. Dopaminergic depletion in Parkinson's disease disrupts the corticostriatal balance leading to increased activity the indirect circuit and reduced activity in the direct circuit. The precise chain of events leading to increased STN activity is not completely understood, but impaired dopaminergic regulation of the GPe, GPi, and STN may be involved. The parkinsonian state is characterized by disruption of the internal balance of the BG leading to hyperactivity in the two main entry points of the network (striatum and STN) and excessive inhibitory output from the GPi. Replacement therapy with standard levodopa creates a further imbalance, producing an abnormal pattern of neuronal discharge and synchronization of neuronal firing that sustain the "off" and "on with dyskinesia" states. The effect of levodopa is robust but short-lasting and converts the parkinsonian BG into a highly unstable system, where pharmacological and compensatory effects act in opposing directions. This creates a scenario that substantially departs from the normal physiological state of the BG.

Nck adaptor proteins control the organization of neuronal circuits important for walking.

The intracellular signaling targets used by mammalian axon guidance receptors to organize the nervous system in vivo are unclear. The Nck1 and Nck2 SH2/SH3 adaptors (collectively Nck) can couple phosphotyrosine (pTyr) signals to reorganization of the actin cytoskeleton and are therefore candidates for linking guidance cues to the regulatory machinery of the cytoskeleton. We find that selective inactivation of Nck in the murine nervous system causes a hopping gait and a defect in the spinal central pattern generator, which is characterized by synchronous firing of bilateral ventral motor neurons. Nck-deficient mice also show abnormal projections of corticospinal tract axons and defective development of the posterior tract of the anterior commissure. These phenotypes are consistent with a role for Nck in signaling initiated by different classes of guidance receptors, including the EphA4 receptor tyrosine kinase. Our data indicate that Nck adaptors couple pTyr guidance signals to cytoskeletal events required for the ipsilateral projections of spinal cord neurons and thus for normal limb movement.

How specific is synchronous neuronal firing?

Synchronous neuronal firing has been discussed as apotential neuronal code. For testing first, if synchronousfiring exists, second if it is modulated by the behaviour,and third if it is not by chance, a large set of tools has beendeveloped. However, to test whether synchronous neuro-nal firing is really involved in information processing oneneeds a direct comparison of the amount of synchronousfiring for different factors like experimental or behav-ioural conditions. To this end we present an extended ver-sion of a previously published method NeuroXidence [1],which tests, based on a bi- and multivariate test design,whether the amount of synchronous firing above thechance level is different for different factors.

Layer and frequency dependencies of phase response properties of pyramidal neurons in rat motor cortex

It is postulated that synchronous firing of cortical neurons plays an active role in cognitive functions of the brain. An important issue is whether pyramidal neurons in different cortical layers exhibit similar tendencies to synchronise. To address this issue, we performed intracellular and whole-cell recordings of regular-spiking pyramidal neurons in slice preparations of the rat motor cortex (18-45 days old) and analysed the phase response curves of these pyramidal neurons in layers 2/3 and 5. The phase response curve represents how an external stimulus affects the timing of spikes immediately after the stimulus in repetitively firing neurons. The phase response curve can be classified into two categories, type 1 (the spike is always advanced) and type 2 (the spike is advanced or delayed depending on the stimulus phase), and are important determinants of whether or not rhythmic synchronization of neuron pairs occurs. We found that pyramidal neurons in layer 2/3 tend to display type-2 phase response curves whereas those in layer 5 tend to exhibit type-1 phase response curves. The differences were prominent particularly in the gamma-frequency range (20-45 Hz). Our results imply that the layer-2/3 pyramidal neurons, when coupled mutually through fast excitatory synapses, may exhibit a much stronger tendency for rhythmic synchronization than layer-5 neurons in the gamma-frequency range.

Beta Rhythms (15–20 Hz) Generated by Nonreciprocal Communication in Hippocampus

Generation of gamma rhythms in reciprocally connected areas of cortex produces synchronous neuronal firing, although little is known about the consequences of gamma rhythms when generated in nonreciprocally connected regions. This nonreciprocity exists in hippocampus, where gamma rhythms are generated in area CA3 in vitro and in vivo and nonreciprocally projected to area CA1 by the Schaffer collateral pathway. Here we demonstrate how this CA3 gamma rhythm generates two different patterns of local CA1 oscillation dependent on the degree of output from area CA1. 1) In conditions where activity projected to area CA1 produces only very low principal cell recruitment the local population rhythm mimics the gamma rhythm projected from CA3. This activity is generated predominantly by recruitment of CA1 basket cells in a manner dependent on phasic, feedforward excitation of this interneuron subclass. Interneurons in stratum oriens, not receiving CA3 feedforward input, fired at theta frequencies. 2) In the presence of serotonin CA1 principal cell recruitment was appreciably enhanced, resulting in dual activation of CA1 basket cells through both feedforward and feedback excitations. Feedback excitation to CA1 stratum oriens interneurons was also enhanced. The resulting change in interneuron network dynamics generated a beta-frequency CA1 rhythm (as a near-subharmonic of the gamma rhythm projected from CA3). These findings demonstrate that in nonreciprocally connected networks, the frequency of population rhythms in target areas serves to code for degree of principal cell recruitment by afferent input.

Learning-Induced Enduring Changes in Functional Connectivity among Prefrontal Cortical Neurons

Current thinking about how memories are stored in the brain has been profoundly influenced by Donald O. Hebb's cell assembly hypothesis, which posits that (1) learning produces a stable alteration in patterns of connectivity among repeatedly coactivated neurons, and (2) memory retrieval involves reactivation of those altered patterns of connectivity. However, learning-induced changes in connectivity that persist over long periods of time have not been clearly demonstrated. In the present study, two spatial navigation tasks and a long-term ensemble recording technique are used to describe long-lasting modifications in functional connectivity (FC) (defined as changes in synchronous firing) of prefrontal cortical neurons in behaving rats. Animals were initially trained to alternate visiting two spatial locations on a figure-8-shaped maze to obtain a reward (alternating task 1). Afterward, while continuing on task 1, animals were additionally trained to visit only one spatial location on the same maze to obtain a reward (unilateral task 2). Multiple single units were recorded while rats were undergoing acquisition, retention, and performance of both tasks. Our data indicate that correlated firing of prefrontal cortical neurons changed significantly in early phases of training when learning rate was maximal but became progressively smaller in later phases when learning reached asymptote. After animals became proficient, FC remained constant, although neuronal activities varied across two different tasks. The present finding of negatively accelerated changes in FC confirms associative learning theories and provides crucial neurophysiological evidence for Hebb's hypothesis.

Molecular Signaling Mechanisms Underlying Epileptogenesis

Epilepsy, a disorder of recurrent seizures, is a common and frequently devastating neurological condition. Available therapy is only symptomatic and often ineffective. Understanding epileptogenesis, the process by which a normal brain becomes epileptic, may help identify molecular targets for drugs that could prevent epilepsy. A number of acquired and genetic causes of this disorder have been identified, and various in vivo and in vitro models of epileptogenesis have been established. Here, we review current insights into the molecular signaling mechanisms underlying epileptogenesis, focusing on limbic epileptogenesis. Study of different models reveals that activation of various receptors on the surface of neurons can promote epileptogenesis; these receptors include ionotropic and metabotropic glutamate receptors as well as the TrkB neurotrophin receptor. These receptors are all found in the membrane of a discrete signaling domain within a particular type of cortical neuron--the dendritic spine of principal neurons. Activation of any of these receptors results in an increase Ca2+ concentration within the spine. Various Ca2+-regulated enzymes found in spines have been implicated in epileptogenesis; these include the nonreceptor protein tyrosine kinases Src and Fyn and a serine-threonine kinase [Ca2+-calmodulin-dependent protein kinase II (CaMKII)] and phosphatase (calcineurin). Cross-talk between astrocytes and neurons promotes increased dendritic Ca2+ and synchronous firing of neurons, a hallmark of epileptiform activity. The hypothesis is proposed that limbic epilepsy is a maladaptive consequence of homeostatic responses to increases of Ca2+ concentration within dendritic spines induced by abnormal neuronal activity.

A single evoked afterdischarge produces rapid time-dependent changes in connexin36 protein expression in adult rat dorsal hippocampus

Gap junctions between neurons contribute to synchronous neuronal firing and may play a role in the pathophysiology of epilepsy. We examined the expression of a number of gap junction subunits, including the neuronal gap junction forming protein connexin36 (Cx36), in the hippocampus at various time points following an electrically stimulated afterdischarge (AD) in freely-moving animals. Once recovered from electrode implantation, animals were tested with an escalating series of stimulations until an AD was evoked. Suprathreshold stimulation produced a brief AD with no convulsion. Groups of animals were sacrificed at 3, 12, and 24 h post-stimulation, and connexin expression was assessed via semiquantitative immunoblotting. Compared to implanted non-stimulated controls, a significant decrease in Cx36 expression was observed in the stimulated dorsal hippocampus at 3 h post-stimulation, which returned to control levels by 24 h. No changes were seen in the ventral hippocampus. As well, no changes were seen in other selected connexin proteins including Cx26, Cx32, and Cx43, thought to be expressed primarily in glia, in either dorsal or ventral hippocampus. These data suggest that a relatively brief hypersynchronous neuronal discharge can produce rapid and specific changes in Cx36 expression, which may have implications for both normal brain function and the pathophysiology of epilepsy.

General Anesthetic-induced Seizures Can Be Explained by a Mean-field Model of Cortical Dynamics

General Anesthetic-induced Seizures Can Be Explained by a Mean-field Model of Cortical Dynamics

KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ/Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 +/- 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30-80 Hz). Further increasing [K+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 microM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991-sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 microM) or XE-991 (10 microM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

The Many Flavors of Temporal Coding in Gustatory Cortex

Environmental stimuli are temporally extensive. They typically (at the very least) wax and wane, and their time-varying aspects are further shaped by the behavioral responses they engender, as animals engage in approach or avoidance. Thus, neural activity related to sensation must be intrinsically time varying as well. Even if sensory stimuli were somehow punctate and static, however, neural activity would still be dynamic, because it is the job of neural brain systems to transform responses to those stimuli into activity appropriate for driving behavior, which itself unfolds as a function of time. These statements, true in general, are particularly true of the gustatory system, where the coupling between perception and action is virtually unbreakable: it is impossible for an awake animal to passively observe a taste stimulus (Grill and Norgren, 1978a; Travers and Norgren, 1986). This fact, and the purely neural evidence of functional feedback and convergence in forebrain and brainstem taste relays (Smith and Li, 2000; Lundy and Norgren, 2004), should lead researchers to expect some sort of temporal coding in gustatory activity. But to say that gustation involves temporal coding is to say little, because the term ‘temporal coding’ means many things to many researchers. To some the phrase connotes ‘fast’ dynamics: the synchronous firing of neurons (e.g. deCharms and Merzenich, 1996; Hatsopoulos et al., 1998; Christensen et al., 2000; Steinmetz et al., 2000) or neural oscillations in the ~10, ~20, or ~40 Hz range (e.g. Eckhorn, 1994; MacLeod et al., 1998). To others, it refers to ‘slower’ rate changes, either in single neurons or among coherent groups of neurons (Seidemann et al., 1996; Friedrich and Laurent, 2004). What shall we say about temporal coding in the gustatory system? Several labs including mine are currently seeking answers to this question. Thus far, the data tell the story of temporal coding being apparent mostly (but not solely) at the level of coherent rate changes among neural ensembles, perhaps driving the system toward (or reflecting) response specification. Gustatory cortical (GC) involvement in this process may extend to preparatory coding that develops across trials in learning situations.

Slow-wave sleep: serotonin, neuronal plasticity, and seizures.

This article starts by enumerating several data that vindicate Michel Jouvet's hypothesis regarding serotonin as a factor promoting slow-wave sleep. The core of the article is devoted to the description of neuronal bases underlying sleep oscillations, with emphasis on the cortically generated slow oscillation (0.5-1 Hz) that groups both low-frequency (spindles and delta) and high-frequency (beta/gamma) rhythms. The low-frequency rhythms are generated by the synchronous firing of cortical neurons during the depolarizing phase of the slow oscillation, which impacts on the thalamic circuitry to generate spindles and clock-like delta potentials. The fast activity is voltage-dependent and occurs during the depolarization component of the slow cortical oscillation. This coalescence of brain rhythms, discovered in intracellular studies of neocortical and thalamic neurons, is now supported by EEG studies during human sleep. The rich spontaneous activity of neocortical neurons during slow-wave sleep is associated with neuronal plasticity that may play a role in consolidating memory traces acquired during the state of waking. Surprisingly, neuronal plasticity, usually regarded as a beneficial phenomenon implicated in memory and learning, could develop during slow-wave sleep into self-sustained paroxysmal discharges, similar to spike-wave complexes that appear in some epileptic syndromes.

Carbonic anhydrase isoform VII acts as a molecular switch in the development of synchronous gamma-frequency firing of hippocampal CA1 pyramidal cells.

Identification of the molecular mechanisms that enable synchronous firing of CA1 pyramidal neurons is central to the understanding of the functional properties of this major hippocampal output pathway. Using microfluorescence measurements of intraneuronal pH, in situ hybridization, as well as intracellular, extracellular, and K+-sensitive microelectrode recordings, we show now that the capability for synchronous gamma-frequency (20-80 Hz) firing in response to high-frequency stimulation (HFS) emerges abruptly in the rat hippocampus at approximately postnatal day 12. This was attributable to a steep developmental upregulation of intrapyramidal carbonic anhydrase isoform VII, which acts as a key molecule in the generation of HFS-induced tonic GABAergic excitation. These results point to a crucial role for the developmental expression of intrapyramidal carbonic anhydrase VII activity in shaping integrative functions, long-term plasticity and susceptibility to epileptogenesis.

Obsessive-compulsive disorder: development of demand-controlled deep brain stimulation with methods from stochastic phase resetting.

Synchronization of neuronal firing is a hallmark of several neurological diseases. Recently, stimulation techniques have been developed which make it possible to desynchronize oscillatory neuronal activity in a mild and effective way, without suppressing the neurons' firing. As yet, these techniques are being used to establish demand-controlled deep brain stimulation (DBS) techniques for the therapy of movement disorders like severe Parkinson's disease or essential tremor. We here present a first conceptualization suggesting that the nucleus accumbens is a promising target for the standard, that is, permanent high-frequency, DBS in patients with severe and chronic obsessive-compulsive disorder (OCD). In addition, we explain how demand-controlled DBS techniques may be applied to the therapy of OCD in those cases that are refractory to behavioral therapies and pharmacological treatment.

Synchrony-dependent propagation of firing rate in iteratively constructed networks in vitro.

The precise role of synchronous neuronal firing in signal encoding remains unclear. To examine what kinds of signals can be carried by synchrony, I reproduced a multilayer feedforward network of neurons in an in vitro slice preparation of rat cortex using an iterative procedure. When constant and time-varying frequency signals were delivered to the network, the firing of neurons in successive layers became progressively more synchronous. Notably, synchrony in the in vitro network developed even with uncorrelated input, persisted under a wide range of physiological conditions and was crucial for the stable propagation of rate signals. The firing rate was represented by a classical rate code in the initial layers, but switched to a synchrony-based code in the deeper layers.

Real-time measurements of phasic changes in extracellular dopamine concentration in freely moving rats by fast-scan cyclic voltammetry.

Rapid, transient changes in extracellular dopamine concentrations following salient stimuli in freely moving rats have recently been detected using fast-scan cyclic voltammetry (1,2). This type of neurotransmission had not been previously observed (for any neurotransmitter), but has been implicated by electrophysiological studies. Schultz et al. (3) reported synchronous burst firing of midbrain dopaminergic neurons following presentation of liquid reinforcers or associated cues. Such firing patterns would predictably produce transient (lasting no more than a few seconds), high concentrations (high nanomolar) of extracellular dopamine in terminal regions. This phasic dopaminergic neurotransmission has been heavily implicated in associative learning and reward processing, and therefore may prove essential in understanding the reinforcing actions of drugs of abuse.

Computation by ensemble synchronization in recurrent networks with synaptic depression.

While computation by ensemble synchronization is considered to be a robust and efficient way for information processing in the cortex (C. Von der Malsburg and W. Schneider (1986) Biol. Cybern. 54: 29-40; W. Singer (1994) Inter. Rev. Neuro. 37: 153-183; J.J. Hopfield (1995) Nature 376: 33-36; E. Vaadia et al. (1995) Nature 373: 515-518), the neuronal mechanisms that might be used to achieve it are yet to be uncovered. Here we analyze a neural network model in which the computations are performed by near coincident firing of neurons in response to external inputs. This near coincident firing is enabled by activity dependent depression of inter-neuron connections. We analyze the network behavior by using a mean-field approximation, which allows predicting the network response to various inputs. We demonstrate that the network is very sensitive to temporal aspects of the inputs. In particular, periodically applied inputs of increasing frequency result in different response profiles. Moreover, applying combinations of different stimuli lead to a complex response, which cannot be easily predicted from responses to individual components. These results demonstrate that networks with synaptic depression can perform complex computations on time-dependent inputs utilizing the ability to generate temporally synchronous firing of single neurons.

Locomotion towards a goal alters the synchronous firing of neurons recorded simultaneously in the subiculum and nucleus accumbens of rats

Rats were implanted with recording electrodes aimed at the subiculum and nucleus accumbens. They were subsequently placed in a cylindrical environment, where they searched for locations where they would receive rewarding medial forebrain bundle stimulation. At times a tone was sounded, indicating that the reward location was in the center of the environment. Animals quickly learned to switch from random running to goal directed locomotion when the tone was on. To quantify the synchronous firing between simultaneously recorded neurons in the subiculum and nucleus accumbens, a gravitational clustering algorithm was employed. Individual neurons were modeled as particles in N dimensional space. Every spike discharge of the neuron augmented the ‘gravitational charge’ on its model particle. Synchronous firing between two cells caused their corresponding particles to draw together over time, due to the concurrent appearance of gravitational charge. All pair-wise combinations of cells isolated in subiculum and nucleus accumbens were examined using this algorithm. The firing of nine out of 52 subicular–accumbens cell pairings was significantly more synchronous when the tone was on, and the rat was running towards the central goal. This was also seen for 15 out of 22 subicular–subicular cell pairings. Conversely, only two out of 51 accumbens–accumbens pairings displayed significant tone dependent changes in synchronous firing. Thus, synchronous interactions between subiculum and nucleus accumbens occur preferentially when the animal is required to locate a fixed goal in space, i.e., the functional connectivity is altered by the navigational demands of the spatial reward task.