It is not totally understood how a seizure focus differs from normal brain. Working with epileptologists and neurosurgeons, we have collected tissue samples from patients who are having surgery to remove abnormal brain regions that generate seizures for treatment of their epilepsy. In this epileptogenic tissue we have found altered gene expression of the circadian transcription factor, Clock. Deletion of the Clock gene in excitatory neurons of the cortex causes spontaneous seizures in mice and our goals in this proposal are 1) to identify the circuitry defects in neurons deficient in Clock, 2) molecular mechanisms of Clock in epilepsy and 3) test whether rescue of circadian defects raises seizure threshold.
