Temporal lobe seizures comprise the majority of focal-onset seizures and are particularly refractory to treatment, indicating the need for new, mechanistically motivated therapies. We are investigating dynamic dysfunction of the corticohippocampal circuit in the context of temporal lobe-onset seizures.

The dentate gyrus is a key structure for information transfer from cerebral cortex to hippocampus and limits propagation of activity throughout the limbic system. Dentate gyrus dysfunction, and consequent corticohippocampal network hyperexcitability, is implicated in the pathogenesis of acquired temporal lobe epilepsy.

  • Is the corticohippocampal circuit hyperexcitable in vivo (as it has been shown to be in slice)?
  • Does the corticohippocampal circuit collapse further when approaching seizure threshold?
  • Is cortical input necessary for onset of epileptiform activity within the hippocampus?

Corticohippocampal circuit dysfunction in epilepsy