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Maintenance and termination of neocortical oscillations by dynamic modulation of intrinsic and synaptic excitability

Published online by Cambridge University Press:  22 January 2007

Flavio Fröhlich
Affiliation:
The Salk Institute, Computational Neurobiology Laboratory, La Jolla, CA, 92037 Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, USA
Maxim Bazhenov
Affiliation:
The Salk Institute, Computational Neurobiology Laboratory, La Jolla, CA, 92037
Igor Timofeev
Affiliation:
Departement of Anatomy and Physiology, School of Medicine, Laval University, Québec, Canada G1K 7P4 The Centre de Recherche Universite Laval Robert-Giffard, Québec, Canada G1J 2G3
Terrence J. Sejnowski
Affiliation:
The Salk Institute, Computational Neurobiology Laboratory, La Jolla, CA, 92037 Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, USA

Abstract

Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe childhood epileptic disorder, is characterized by episodes of seizure with alternating epochs of spike-wave and fast run discharges. In a detailed computational model that incorporates extracellular potassium dynamics, we studied the dynamics of these state transitions between slow and fast oscillations. We show that dynamic modulation of synaptic transmission can cause termination of paroxysmal activity. An activity-dependent shift in the balance between synaptic excitation and inhibition towards more excitation caused seizure termination by favoring the slow oscillatory state, which permits recovery of baseline extracellular potassium concentration. We found that slow synaptic depression and change in chloride reversal potential can have similar effects on the seizure dynamics. Our results indicate a novel role for synaptic dynamics during epileptic neural activity patterns.

Type
Research Article
Copyright
© 2007 Cambridge University Press

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