Mossy fiber sprouting interacts with sodium channel mutations to increase dentate gyrus excitability
Evan A Thomas, Christopher A Reid, Steven Petrou
EPILEPSIA | WILEY | Published : 2010
PURPOSE: Idiopathic epilepsy is caused by the complex interaction of genetic and environmental factors. The purpose of this study was to use computational approaches to explore the interaction between changes in sodium channel availability caused by mutations and mossy fiber sprouting. METHODS: We used a previously published biophysically realistic computer model of dentate gyrus neurons and networks. A sensitivity analysis probed the effects of typical mutation-like changes in either single- or multiple-gating parameters. Isolated neuron models were stimulated with current injections, and networks were stimulated with perforant path synaptic input. The gene-environment interaction was studi..View full abstract
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Awarded by Australian National Health and Medical Research Council
EAT was partially supported by an Australian National Health and Medical Research Council Peter Doherty Fellowship. CAR was supported by a University of Melbourne RD Wright Fellowship and by Australian National Health and Medical Research Council project grant 454655. Aspects of this work were also supported by an Australian National Health and Medical Research Council program grant 400121. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.Disclosure: None of the authors has any conflict of interest to disclose.