期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 39, 页码 13448-13462出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5038-14.2015
关键词
epileptic seizures; homeostatic plasticity; ion concentration dynamics; network models; synaptic plasticity
资金
- National Institutes of Health Grants [R01EB009282, R01NS081243]
- Office of Naval Research Multidisciplinary University Research Initiative Grant [N000141310672]
- Canadian Institutes of Health Research Grants [201403MOP-325213, 201403MOP-324941]
- National Science Foundation Graduate Research Fellowship Grant [DGE-1326120]
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.
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