Excitatory Synaptic Coupling Research Articles

The relationship between synchronization phenomena, firing and synaptic dynamics in synaptically interconnected neuron models

In this Letter, a new type of neuronal firing model is proposed. Using this model, conditions for the occurrence of in-phase as well as anti-phase synchronized oscillations are investigated in terms of the parameters representing rising and decaying relaxation rates of synaptic couplings. Then, it is examined whether neuronal spiking of a system with excitatory or inhibitory synaptic couplings which occurs in the new model, is dependent on synaptic response. We will then compare our findings to previous results. In comparison to our previous study, we now suggest that occurrence of the synchronization phenomena depend on specific properties of neuronal firing dynamics.

Modulation of excitatory synaptic coupling facilitates synchronization and complex dynamics in a biophysical model of neuronal dynamics

In this paper, complex dynamical synchronization in a non-linear model of a neural system is studied, and the computational significance of the behaviours is explored. The local neural dynamics is determined by voltage- and ligand-gated ion channels and feedback between densely interconnected excitatory and inhibitory neurons. A mesoscopic array of local networks is modelled by introducing coupling between the local networks via weak excitatory-to-excitatory connectivity. It is shown that with modulation of this long-range synaptic coupling, the system undergoes a transition from independent oscillations to stable chaotic synchronization. Between these states exists a 'weakly' stable state associated with complex, intermittent behaviour in the temporal domain and clusters of synchronous regions in the spatial domain. The paper concludes with a discussion of the putative relevance of such processes in the brain, including the role of neuromodulatory systems and the mechanisms underlying sensory perception, adaptation, computation and complexity.

Modulation of excitatory synaptic coupling facilitates synchronization and complex dynamics in a nonlinear model of neuronal dynamics

We study dynamical synchronization in a model of a neural system constituted by local networks of densely interconnected excitatory and inhibitory neurons. Neural dynamics are determined by voltage- and ligand-gated ion channels. Coupling between the local networks is introduced via sparse excitatory connectivity. With modulation of this long-range synaptic coupling the system undergoes a transition from independent oscillations to chaotic synchronization. Between these states exists a 'weakly’ stable state with epochs of synchronization and complex intermittent desynchronization. This may facilitate adaptive brain function by engendering a diverse repertoire of dynamics and contribute to the genesis of complexity in the EEG.

Modulation of excitatory synaptic coupling facilitates synchronization and complex dynamics in a biophysical model of neuronal dynamics

In this paper, complex dynamical synchronization in a non-linear model of a neural system is studied, and the computational significance of the behaviours is explored. The local neural dynamics is determined by voltage-and ligand-gated ion channels and feedback between densely interconnected excitatory and inhibitory neurons. A mesoscopic array of local networks is modelled by introducing coupling between the local networks via weak excitatory-to-excitatory connectivity. It is shown that with modulation of this long-range synaptic coupling, the system undergoes a transition from independent oscillations to stable chaotic synchronization. Between these states exists a ‘weakly’ stable state associated with complex, intermittent behaviour in the temporal domain and clusters of synchronous regions in the spatial domain. The paper concludes with a discussion of the putative relevance of such processes in the brain, including the role of neuromodulatory systems and the mechanisms underlying sensory perception, adaptation, computation and complexity.

Spiking neuron models with excitatory or inhibitory synaptic couplings and synchronization phenomena.

We investigate synchronization phenomena in a system of two piecewise-linear-type model neurons with excitatory or inhibitory synaptic couplings. Employing the phase plane analysis and a singular perturbation approach to split the dynamics into slow and fast ones, we construct analytically the Poincaré map of the solution to the piecewise-linear equations. We investigate conditions for the occurrence of synchronized oscillations of in phase as well as of antiphase in terms of parameters representing the strength of the synaptic coupling and the decaying relaxation rate of the synaptic dynamics. We present the results of numerical simulations that agree with our theoretical ones.

Synchronized Activity and Loss of Synchrony Among Heterogeneous Conditional Oscillators

The inspiratory phase of the respiratory rhythm involves the synchronized bursting of a network of neurons in the brain stem. This paper considers activity patterns in a reduced model for this network, namely, a system of conductance-based ordinary differential equations with excitatory synaptic coupling, incorporating heterogeneities across cells. The model cells are relaxation oscillators; that is, no spikes are included. In the continuum limit, under assumptions based on the disparate time scales in the model, we derive consistency conditions sufficient to give tightly synchronized oscillations; when these hold, we solve a fixed point equation to find a unique synchronized periodic solution. This solution is stable within a certain solution class, and we provide a general sufficient condition for its stability. Allowing oscillations that are less cohesive but still synchronized, we derive an ordinary differential equation boundary value problem that we solve numerically to find a corresponding periodic solution. These results help explain how heterogeneities among synaptically coupled oscillators can enhance the tendency toward synchronization of their activity. Finally, we consider conditions for synchrony to break down.

Models of Respiratory Rhythm Generation in the Pre-Bötzinger Complex. III. Experimental Tests of Model Predictions

We used the testable predictions of mathematical models proposed by Butera et al. to evaluate cellular, synaptic, and population-level components of the hypothesis that respiratory rhythm in mammals is generated in vitro in the pre-Bötzinger complex (pre-BötC) by a heterogeneous population of pacemaker neurons coupled by fast excitatory synapses. We prepared thin brain stem slices from neonatal rats that capture the pre-BötC and maintain inspiratory-related motor activity in vitro. We recorded pacemaker neurons extracellularly and found: intrinsic bursting behavior that did not depend on Ca(2+) currents and persisted after blocking synaptic transmission; multistate behavior with transitions from quiescence to bursting and tonic spiking states as cellular excitability was increased via extracellular K(+) concentration ([K(+)](o)); a monotonic increase in burst frequency and decrease in burst duration with increasing [K(+)](o); heterogeneity among different cells sampled; and an increase in inspiratory burst duration and decrease in burst frequency by excitatory synaptic coupling in the respiratory network. These data affirm the basis for the network model, which is composed of heterogeneous pacemaker cells having a voltage-dependent burst-generating mechanism dominated by persistent Na(+) current (I(NaP)) and excitatory synaptic coupling that synchronizes cell activity. We investigated population-level activity in the pre-BötC using local "macropatch" recordings and confirmed these model predictions: pre-BötC activity preceded respiratory-related motor output by 100-400 ms, consistent with a heterogeneous pacemaker-cell population generating inspiratory rhythm in the pre-BötC; pre-BötC population burst amplitude decreased monotonically with increasing [K(+)](o) (while frequency increased), which can be attributed to pacemaker cell properties; and burst amplitude fluctuated from cycle to cycle after decreasing bilateral synaptic coupling surgically as predicted from stability analyses of the model. We conclude that the pacemaker cell and network models explain features of inspiratory rhythm generation in vitro.

Synaptic reorganization in explanted cultures of rat hippocampus

Due to loss of afferent innervation, synaptic reorganization occurs in organotypic hippocampal slice cultures. With extra- and intracellular recordings, we confirm that the excitatory loop from the dentate gyrus (DG) to CA3 and further to CA1 is preserved. However, hilar stimulation evoked antidromic population spikes in the DG which were followed by a population postsynaptic potential (PPSP); intracellularly, an antidromic spike with a broad shoulder or EPSP/IPSP sequences were induced. Synaptic responses were blocked by glutamate receptor antagonists. Stimulation of CA1 induced a PPSP in DG. Dextranamine stained pyramidal cells of CA1 were shown to project to DG. After removal of area CA3, DG's and mossy fibers' (MF) stimulation still elicited PPSPs and EPSP/IPSP sequences in area CA1 which disappeared when a cut was made through the hippocampal fissure. During bicuculline perfusion, hilar stimulation caused EPSPs in granule cells and spontaneous and evoked repetitive firing appeared even after its isolation from areas CA3 and CA1. Collateral excitatory synaptic coupling between granule cells was confirmed by paired recordings. Besides the preservation of the trisynaptic pathway in this preparation, new functional synaptic contacts appear, presumably due to MF collateral sprouting and formation of pathways between areas CA1 and DG.

Computer simulations of stimulus dependent state switching in basic circuits of bursting neurons

We investigate the ability of oscillating neural circuits to switch between different states of oscillation in two basic neural circuits. We model two quite distinct small neural circuits. The first circuit is based on invertebrate central pattern generator (CPG) studies [A. I. Selverston and M. Moulins, The Crustacean Stomatogastric System (Springer-Verlag, Berlin, 1987)] and is composed of two neurons coupled via both gap junction and inhibitory synapses. The second consists of coupled pairs of interconnected thalamocortical relay and thalamic reticular neurons with both inhibitory and excitatory synaptic coupling. The latter is an elementary unit of the thalamic networks passing sensory information to the cerebral cortex [M. Steriade, D. A. McCormick, and T. J. Sejnowski, Science 262, 679 (1993)]. Both circuits have contradictory coupling between symmetric parts. The thalamocortical model has excitatory and inhibitory connections and the CPG has reciprocal inhibitory and electrical coupling. We describe the dynamics of the individual neurons in these circuits by conductance based ordinary differential equations of Hodgkin-Huxley type [J. Physiol. (London) 117, 500 (1952)]. Both model circuits exhibit bistability and hysteresis in a wide region of coupling strengths. The two main modes of behavior are in-phase and out-of-phase oscillations of the symmetric parts of the network. We investigate the response of these circuits, while they are operating in bistable regimes, to externally imposed excitatory spike trains with varying interspike timing and small amplitude pulses. These are meant to represent spike trains received by the basic circuits from sensory neurons. Circuits operating in a bistable region are sensitive to the frequency of these excitatory inputs. Frequency variations lead to changes from in-phase to out-of-phase coordination or vice versa. The signaling information contained in a spike train driving the network can place the circuit into one or another state depending on the interspike interval and this happens within a few spikes. These states are maintained by the basic circuit after the input signal is ended. When a new signal of the correct frequency enters the circuit, it can be switched to another state with the same ease.

Global competition and local cooperation in a network of neural oscillators

An architecture of locally excitatory, globally inhibitory oscillator networks is proposed and investigated both analytically and by computer simulation. The model for each oscillator corresponds to a standard relaxation oscillator with two time scales. Oscillators are locally coupled by a scheme that resembles excitatory synaptic coupling, and each oscillator also inhibits other oscillators through a common inhibitor. Oscillators are driven to be oscillatory by external stimulation. The network exhibits a mechanism of selective gating, whereby an oscillator jumping up to its active phase rapidly recruits the oscillators stimulated by the same pattern, while preventing the other oscillators from jumping up. We show analytically that with the selective gating mechanism, the network rapidly achieves both synchronization within blocks of oscillators that are stimulated by connected regions and desynchronization between different blocks. Computer simulations demonstrate the model's promising ability for segmenting multiple input patterns in real time. This model lays a physical foundation for the oscillatory correlation theory of feature binding and may provide an effective computational framework for scene segmentation and figure/ ground segregation.

When inhibition not excitation synchronizes neural firing.

Excitatory and inhibitory synaptic coupling can have counter-intuitive effects on the synchronization of neuronal firing. While it might appear that excitatory coupling would lead to synchronization, we show that frequently inhibition rather than excitation synchronizes firing. We study two identical neurons described by integrate-and-fire models, general phase-coupled models or the Hodgkin-Huxley model with mutual, non-instantaneous excitatory or inhibitory synapses between them. We find that if the rise time of the synapse is longer than the duration of an action potential, inhibition not excitation leads to synchronized firing.

Strategies for the development of drugs for pharmacoresistant epilepsies.

Presently, most strategies for development of antiepileptic drugs (AEDs) center around seizure models that are known to respond to presently marketed AEDs. These strategies do not take into account that epilepsy can be a progressive disease. Moreover, region-specific aspects of epileptogenesis are rarely considered when new AEDs are developed. Seizures in the temporal lobe are often difficult to treat. Animal studies on various seizure models in the hippocampus and the entorhinal cortex (EC) suggest that these structures do not a priori produce seizures that are difficult to treat. However, seizure-like events in the EC tend to progress to a state of status epilepticus-like activity that cannot be suppressed by presently marketed AEDs. Loss of gamma-aminobutyric acid (GABA)ergic neurotransmission and increased excitatory synaptic coupling seem to cooperate for induction of this state. Epilepsy induced alterations in the interaction between the EC and the hippocampus may lead to alterations that facilitate precipitation of seizures. Because of the recurrent interaction between the hippocampus and the EC, these seizures may reach an intensity that is no longer controllable by presently available AEDs. Ontogenetic alterations of the circuitry between the EC and the hippocampus, seizure-induced stabilization of synaptic connections overexpressed during ontogenesis, seizure-induced lesions and subsequent rearrangements of internal cell properties, and synaptic arrangements and kindling-like alterations of nerve cell and glial behavior may all be involved in the generation of a neuronal aggregate whose balance between inhibitory and excitatory processes becomes readily disturbed. Strategies for the development of AEDs treating such seizures should suppress hyperactivity and prevent progression of epileptogenesis. AEDs directed against seizures may be effective if they can be given in sufficient concentrations to suppress very intense local seizures.

Mechanisms of epileptogenesis in cortical structures.

Studies of the mechanisms of epileptogenesis in brain-slice model systems have emphasized the role of three interacting processes in the development of interictal discharge. These processes are intrinsic burst activity, disinhibition, and excitatory synaptic coupling. Intrinsic membrane excitability may be altered by neuromodulators, injury, genetic mutations, and other factors. Disinhibition releases intrinsic burst-generating capacities in subpopulations of neurons and may become an important factor following cortical injury or repetitive activation of inhibitory circuits. Excitatory synaptic coupling is required in order to synchronize populations of neurons. Synaptic currents also serve as a major generator of slow depolarization shifts in individual neurons. The contribution of each of these factors to epileptogenesis may vary with the type of pathological process and the properties of the specific neuronal population.

Certains aspects de la physiologie et de la pathophysiologie des fuseaux chez le chat

Spindles are a thalamocortical rhythm entirely dependent upon a thalamic mechanism. Generators of cortical spindle waves are the pyramidal neurons of the cortex. A positive statistical relationship exists between postsynaptic excitatory events of these neurons and spindle waves, but there is no significant association with inhibitory postsynaptic events. The excitatory synaptic coupling between thalamocortical fibers and cortical neurons implicated in the genesis of spindles is weak, but increases considerably after i.m. injection of penicillin which induces a transformation of spindles into generalized spike and wave discharges (feline generalized penicillin epilepsy). The bursts of increased discharges of pyramidal neurons after penicillin recruit the recurrent intracortical inhibitory pathway. There results from this an oscillation between phases of increased excitability and phases of diminished excitability which correspond respectively to the spike and to the slow wave component of the spike and wave complex. In its turn the cortex imposes this pattern of discharge upon the thalamus which brings about a close coupling of cortical and thalamic neuronal discharges during spike and wave activity.

Penicillin as an epileptogenic agent: effect on an isolated synapse.

Penicillin enhances the excitatory postsynaptic potential of the squid stellate ganglion. This effect suggests the hypothesis that the epileptic focus created by the topical application of penicillin to the mammalian cerebral cortex is produced by the facilitation of excitatory synaptic coupling within the preexisting positive recurrent feedback system.