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Your search keyword '"Savtchenko, Leonid P."' showing total 150 results
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150 results on '"Savtchenko, Leonid P."'

1. Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network.

Author

Magloire, Vincent, Savtchenko, Leonid, Jensen, Thomas, Sylantyev, Sergyi, Kopach, Olga, Cole, Nicholas, Tyurikova, Olga, Kullmann, Dimitri, Walker, Matthew, Marvin, Jonathan, Hasseman, Jeremy, Kolb, Ilya, Pavlov, Ivan, Rusakov, Dmitri, and Looger, Loren

Subjects
GABA uptake, GAT-1, brain rhythms, epilepsy, extracellular GABA, iGABASnFR2, spiking neural networks, tonic GABA conductance, volume transmission, Hippocampus, Synaptic Transmission, Neurons, Interneurons, gamma-Aminobutyric Acid
Abstract

Mechanisms that entrain and pace rhythmic epileptiform discharges remain debated. Traditionally, the quest to understand them has focused on interneuronal networks driven by synaptic GABAergic connections. However, synchronized interneuronal discharges could also trigger the transient elevations of extracellular GABA across the tissue volume, thus raising tonic conductance (Gtonic) of synaptic and extrasynaptic GABA receptors in multiple cells. Here, we monitor extracellular GABA in hippocampal slices using patch-clamp GABA sniffer and a novel optical GABA sensor, showing that periodic epileptiform discharges are preceded by transient, region-wide waves of extracellular GABA. Neural network simulations that incorporate volume-transmitted GABA signals point to a cycle of GABA-driven network inhibition and disinhibition underpinning this relationship. We test and validate this hypothesis using simultaneous patch-clamp recordings from multiple neurons and selective optogenetic stimulation of fast-spiking interneurons. Critically, reducing GABA uptake in order to decelerate extracellular GABA fluctuations-without affecting synaptic GABAergic transmission or resting GABA levels-slows down rhythmic activity. Our findings thus unveil a key role of extrasynaptic, volume-transmitted GABA in pacing regenerative rhythmic activity in brain networks.

Published
2023

28. Astroglial biophysics probed with a realistic cell model

Author

Savtchenko, Leonid P., primary, Bard, Lucie, additional, Jensen, Thomas P., additional, Reynolds, James P., additional, Kraev, Igor, additional, Medvedev, Mikola, additional, Stewart, Michael G., additional, Henneberger, Christian, additional, and Rusakov, Dmitri A., additional

Published
2018
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32. Regulation of rhythm genesis by volume-limited, astroglia-like signals in neural networks

Author

Savtchenko, Leonid P. and Rusakov, Dmitri A.

Subjects
Periodicity, neural network, Pyramidal Cells, Models, Neurological, Computational Biology, Articles, Hippocampus, Synaptic Transmission, astrocyte, nervous system, Astrocytes, basket cell, Humans, Computer Simulation, Nerve Net, Research Article, Signal Transduction
Abstract

Rhythmic activity of the brain often depends on synchronized spiking of interneuronal networks interacting with principal neurons. The quest for physiological mechanisms regulating network synchronization has therefore been firmly focused on synaptic circuits. However, it has recently emerged that synaptic efficacy could be influenced by astrocytes that release signalling molecules into their macroscopic vicinity. To understand how this volume-limited synaptic regulation can affect oscillations in neural populations, here we explore an established artificial neural network mimicking hippocampal basket cells receiving inputs from pyramidal cells. We find that network oscillation frequencies and average cell firing rates are resilient to changes in excitatory input even when such changes occur in a significant proportion of participating interneurons, be they randomly distributed or clustered in space. The astroglia-like, volume-limited regulation of excitatory synaptic input appears to better preserve network synchronization (compared with a similar action evenly spread across the network) while leading to a structural segmentation of the network into cell subgroups with distinct firing patterns. These observations provide us with some previously unknown insights into the basic principles of neural network control by astroglia.

Published
2014

33. Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

Author

Pavlov, Ivan, Savtchenko, Leonid P., Song, Inseon, Koo, Jaeyeon, Pimashkin, Alexey, Rusakov, Dmitri A., and Semyanov, Alexey

Subjects
Male, Neurons, Patch-Clamp Techniques, Time Factors, musculoskeletal, neural, and ocular physiology, Pyramidal Cells, fungi, Models, Neurological, Gramicidin, Action Potentials, Brain, Excitatory Postsynaptic Potentials, Biological Sciences, Receptors, GABA-A, CA3 Region, Hippocampal, Models, Biological, Synaptic Transmission, Rats, Rats, Sprague-Dawley, nervous system, Interneurons, Oscillometry, Animals, gamma-Aminobutyric Acid, Signal Transduction
Abstract

The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABAA conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABAA depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABAA conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABAA conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABAA conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns.

Published
2013

34. Zinc Dynamics and Action at Excitatory Synapses

Author

Vergnano, Angela Maria, primary, Rebola, Nelson, additional, Savtchenko, Leonid P., additional, Pinheiro, Paulo S., additional, Casado, Mariano, additional, Kieffer, Brigitte L., additional, Rusakov, Dmitri A., additional, Mulle, Christophe, additional, and Paoletti, Pierre, additional

Published
2014
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49. Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network.

Author

Pavlov, Ivan, Savtchenko, Leonid P., Inseon Song, Jaeyeon Koo, Pimashkin, Alexey, Rusakov, Dmitri A., and Semyanov, Alexey

Subjects
*GABA, *ELECTRIC admittance, *INTERNEURONS, *EXCITATORY postsynaptic potential, *BRAIN waves
Abstract

The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABAA conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABAA depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABAA conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABAA conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABAA conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns. [ABSTRACT FROM AUTHOR]

Published
2014
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50. Retrograde Synaptic Signaling Mediated by K+ Efflux through Postsynaptic NMDA Receptors.

Author

Shih, Pei-Yu, Savtchenko, Leonid P., Kamasawa, Naomi, Dembitskaya, Yulia, McHugh, Thomas J., Rusakov, Dmitri A., Shigemoto, Ryuichi, and Semyanov, Alexey

Abstract

Summary: Synaptic NMDA receptors (NMDARs) carry inward Ca2+ current responsible for postsynaptic signaling and plasticity in dendritic spines. Whether the concurrent K+ efflux through the same receptors into the synaptic cleft has a physiological role is not known. Here, we report that NMDAR-dependent K+ efflux can provide a retrograde signal in the synapse. In hippocampal CA3-CA1 synapses, the bulk of astrocytic K+ current triggered by synaptic activity reflected K+ efflux through local postsynaptic NMDARs. The local extracellular K+ rise produced by activation of postsynaptic NMDARs boosted action potential-evoked presynaptic Ca2+ transients and neurotransmitter release from Schaffer collaterals. Our findings indicate that postsynaptic NMDAR-mediated K+ efflux contributes to use-dependent synaptic facilitation, thus revealing a fundamental form of retrograde synaptic signaling. [Copyright &y& Elsevier]

Published
2013
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