TrkB in status epilepticus-induced LTP of the mossy fiber-CA3 synapse

Duke University, Durham NC

Investigators

Abstract

DESCRIPTION (provided by applicant): An episode of continuous seizure activity, status epilepticus, is sufficient to induce temporal lobe epilepsy. Recent work has identified activation of TrkB kinase as a molecular mechanism by which an episode of status epilepticus induces lifelong temporal lobe epilepsy; however, the cellular consequences of this TrkB activation that transform the brain from normal to epileptic have not been identified. Enhanced efficacy of excitatory synaptic transmission (long-term potentiation [LTP]) between principal neurons of the limbic system has long been advanced as one mechanism underlying temporal lobe epilepsy. Moreover, the mossy fiber-CA3 synapse in the hippocampus undergoes long-term potentiation after status epilepticus, a synaptic plasticity that could contribute to the epileptic brain. Circumstantial evidence leads me to hypothesize that status epilepticus-induced LTP of this synapse requires activation of TrkB. The objective of my proposal is to test this hypothesis using a combination of a chemical-genetic method with cellular electrophysiological and optogenetic studies of hippocampal slices isolated from an animal model. Successful completion of the proposed work promises to shed light on putative cellular consequences of TrkB activation that underlie development of temporal lobe epilepsy.