Maxim Bazhenov

Model of Transient Oscillatory Synchronization in the Locust Antennal Lobe

Transient pairwise synchronization of locust antennal lobe (AL) projection neurons (PNs) occurs during odor responses. In a Hodgkin-Huxley-type model of the AL, interactions between excitatory PNs and inhibitory local neurons (LNs) created coherent network oscillations during odor stimulation. GABAergic interconnections between LNs led to competition among them such that different groups of LNs oscillated with periodic Ca(2+) spikes during different 50-250 ms temporal epochs, similar to those recorded in vivo. During these epochs, LN-evoked IPSPs caused phase-locked, population oscillations in sets of postsynaptic PNs. The model shows how alternations of the inhibitory drive can temporally encode sensory information in networks of neurons without precisely tuned intrinsic oscillatory properties.

Self-sustained rhythmic activity in the thalamic reticular nucleus mediated by depolarizing GABAA receptor potentials.

Intracellular recordings from reticular thalamic (RE) neurons in vivo revealed inhibitory postsynaptic potentials (IPSPs) between RE cells that reversed and became depolarizing at the hyperpolarized membrane potentials that occur during sleep. These excitatory IPSPs can directly trigger low–threshold spikes (LTSs). The oscillatory mechanisms underlying IPSP–triggered LTSs crowned by spike bursts were investigated in models of isolated RE networks. In a one–dimensional network model, external stimulation evoked waves of excitation propagating at a constant velocity of 25–150 cells per second. In a large–scale, two–dimensional model of the reticular nucleus, the network showed transient or self–sustained oscillations controlled by the maximum conductance of the low–threshold calcium current and the membrane potential. This model predicts that the isolated reticular nucleus could initiate sequences of spindle oscillations in thalamocortical networks in vivo.

Model of Cellular and Network Mechanisms for Odor-Evoked Temporal Patterning in the Locust Antennal Lobe

Locust antennal lobe (AL) projection neurons (PNs) respond to olfactory stimuli with sequences of depolarizing and hyperpolarizing epochs, each lasting hundreds of milliseconds. A computer simulation of an AL network was used to test the hypothesis that slow inhibitory connections between local neurons (LNs) and PNs are responsible for temporal patterning. Activation of slow inhibitory receptors on PNs by the same GABAergic synapses that underlie fast oscillatory synchronization of PNs was sufficient to shape slow response modulations. This slow stimulus- and neuron-specific patterning of AL activity was resistant to blockade of fast inhibition. Fast and slow inhibitory mechanisms at synapses between LNs and PNs can thus form dynamical PN assemblies whose elements synchronize transiently and oscillate collectively, as observed not only in the locust AL, but also in the vertebrate olfactory bulb.

Oscillations in Large-Scale Cortical Networks: Map-Based Model

We develop a new computationally efficient approach for the analysis of complex large-scale neurobiological networks. Its key element is the use of a new phenomenological model of a neuron capable of replicating important spike pattern characteristics and designed in the form of a system of difference equations (a map). We developed a set of map-based models that replicate spiking activity of cortical fast spiking, regular spiking and intrinsically bursting neurons. Interconnected with synaptic currents these model neurons demonstrated responses very similar to those found with Hodgkin-Huxley models and in experiments. We illustrate the efficacy of this approach in simulations of one- and two-dimensional cortical network models consisting of regular spiking neurons and fast spiking interneurons to model sleep and activated states of the thalamocortical system. Our study suggests that map-based models can be widely used for large-scale simulations and that such models are especially useful for tasks where the modeling of specific firing patterns of different cell classes is important.

Intrinsic and Circuit Properties Favor Coincidence Detection for Decoding Oscillatory Input

In the insect olfactory system the antennal lobe generates oscillatory synchronization of its output as a framework for coincidence detection by its target, the mushroom body (MB). The intrinsic neurons of the MB (Kenyon cells, KCs) are thus a good model system in which to investigate the functional relevance of oscillations and neural synchronization. We combine electrophysiological and modeling approaches to examine how intrinsic and circuit properties might contribute to the preference of KCs for coincident input and how their decoding of olfactory information is affected by the absence of oscillatory synchronization in their input. We show that voltage-dependent subthreshold properties of KCs bring about a supralinear summation of their inputs, favoring responses to coincident EPSPs. Abolishing oscillatory synchronization weakens the preference of KCs for coincident input and causes a large reduction in their odor specificity. Finally, we find that a decoding strategy that is based on coincidence detection enhances both noise tolerance and input discriminability by KCs.

Potassium Dynamics in the Epileptic Cortex: New Insights on an Old Topic

The role of changes in the extracellular potassium concentration [K+]o in epilepsy has remained unclear. Historically, it was hypothesized that [K+] o is the causal factor for epileptic seizures. This so-called potassium accumulation hypothesis led to substantial debate but subsequently failed to find wide acceptance. However, recent studies on the pathophysiology of tissue from epileptic human patients and animal epilepsy models revealed aberrations in [K+]o regulation. Computational models of cortical circuits that include ion concentration dynamics have catalyzed a renewed interest in the role of [K+]o in epilepsy. The authors here connect classical and more recent insights on [K+] o dynamics in the cortex with the goal of providing starting points for a next generation of [K+]o research. Such research may ultimately lead to an entirely new class of antiepileptic drugs that act on the [K+]o regulation system. NEUROSCIENTIST 14(5):422—433, 2008. DOI: 10.1177/1073858408317955

Ionic Dynamics Mediate Spontaneous Termination of Seizures and Postictal Depression State

Epileptic seizures are characterized by periods of recurrent, highly synchronized activity that spontaneously terminates, followed by postictal state when neuronal activity is generally depressed. The mechanisms for spontaneous seizure termination and postictal depression remain poorly understood. Using a realistic computational model, we demonstrate that termination of seizure and postictal depression state may be mediated by dynamics of the intracellular and extracellular ion concentrations. Spontaneous termination was linked to progressive increase of intracellular sodium concentration mediated by activation of sodium channels during highly active epileptic state. In contrast, an increase of intracellular chloride concentration extended seizure duration making possible long-lasting epileptic activity characterized by multiple transitions between tonic and clonic states. After seizure termination, the extracellular potassium was reduced below baseline, resulting in postictal depression. Our study suggests that the coupled dynamics of sodium, potassium, and chloride ions play a critical role in the development and termination of seizures. Findings from this study could help identify novel therapeutics for seizure disorder.

Adaptive regulation of sparseness by feedforward inhibition

In the mushroom body of insects, odors are represented by very few spikes in a small number of neurons, a highly efficient strategy known as sparse coding. Physiological studies of these neurons have shown that sparseness is maintained across thousand-fold changes in odor concentration. Using a realistic computational model, we propose that sparseness in the olfactory system is regulated by adaptive feedforward inhibition. When odor concentration changes, feedforward inhibition modulates the duration of the temporal window over which the mushroom body neurons may integrate excitatory presynaptic input. This simple adaptive mechanism could maintain the sparseness of sensory representations across wide ranges of stimulus conditions.

Corticothalamic Feedback Controls Sleep Spindle Duration In Vivo

Spindle oscillations are commonly observed during stage 2 of non-rapid eye movement sleep. During sleep spindles, the cerebral cortex and thalamus interact through feedback connections. Both initiation and termination of spindle oscillations are thought to originate in the thalamus based on thalamic recordings and computational models, although some in vivo results suggest otherwise. Here, we have used computer modeling and in vivo multisite recordings from the cortex and the thalamus in cats to examine the involvement of the cortex in spindle oscillations. We found that although the propagation of spindles depended on synaptic interaction within the thalamus, the initiation and termination of spindle sequences critically involved corticothalamic influences.

Cortical hyperpolarization-activated depolarizing current takes part in the generation of focal paroxysmal activities

During paroxysmal neocortical oscillations, sudden depolarization leading to the next cycle occurs when the majority of cortical neurons are hyperpolarized. Both the Ca2+-dependent K+ currents (IK(Ca)) and disfacilitation play critical roles in the generation of hyperpolarizing potentials. In vivo experiments and computational models are used here to investigate whether the hyperpolarization-activated depolarizing current (Ih) in cortical neurons also contributes to the generation of paroxysmal onsets. Hyperpolarizing current pulses revealed a depolarizing sag in ≈20% of cortical neurons. Intracellular recordings from glial cells indirectly indicated an increase in extracellular potassium concentration ([K+]o) during paroxysmal activities, leading to a positive shift in the reversal potential of K+-mediated currents, including Ih. In the paroxysmal neocortex, ≈20% of neurons show repolarizing potentials originating from hyperpolarizations associated with depth-electroencephalogram positive waves of spike-wave complexes. The onset of these repolarizing potentials corresponds to maximal [K+]o as estimated from dual simultaneous impalements from neurons and glial cells. Computational models showed how, after the increased [K+]o, the interplay between Ih, IK(Ca), and a persistent Na+ current, INa(P), could organize paroxysmal oscillations at a frequency of 2–3 Hz.