Aberrant excitatory connectivity is one mechanism hypothesized to underlie seizure generation in models of hippocampal and neocortical injury and human brain. This proposal will investigate if excitatory circuits are reorganized following a neocortical lesion. Anatomical and electrophysiological techniques will be used to determine specifically the change in excitatory inputs to the soma of layer V pyramidal cells in response to cortical injury. The proposal will also test the efficacy of gabapentin, a commonly prescribed anticonvulsant, to block injury- induced enhanced excitatory circuitry. The proposal will investigate if enhanced excitatory perisomatic connectivity is one mechanism contributing to seizure generation following brain injury, and test if gabapentin can prevent seizure generation by blocking injury-induced enhanced excitatory connectivity.
There is currently no strategy to prevent epilepsy following traumatic brain injury. This proposal will investigate if aberrant excitatory connectivity is one mechanism underlying injury-induced seizures. The proposal will also investigate if gabapentin can prevent injury-induced seizures by blocking changes in excitatory connectivity that follows injury.
|Takahashi, D Koji; Gu, Feng; Parada, Isabel et al. (2016) Aberrant excitatory rewiring of layer V pyramidal neurons early after neocortical trauma. Neurobiol Dis 91:166-81|
|Mantoan Ritter, Laura; Golshani, Peyman; Takahashi, Koji et al. (2014) WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis. Epilepsia 55:1693-702|