Modeling of age-dependent epileptogenesis by differential homeostatic synaptic scaling

Authors: González, Oscar C.; Krishnan, Giri P.; Chauvette, SylvainTimofeev, Igor; Sejnowski, Terrence J.; Bazhenov, Maxim
Abstract: Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals.
Document Type: Article de recherche
Issue Date: 30 September 2015
Open Access Date: 11 May 2017
Document version: VoR
This document was published in: The Journal of neuroscience, Vol. 35 (39), 13448-13462 (2015)
Society of Neuroscience
Alternative version: 10.1523/JNEUROSCI.5038-14.2015
Collection:Articles publiés dans des revues avec comité de lecture

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