Grant: Operating Grant

Seizures are unpredictable events during which the brain activity changes into a pathological state that is associated to abnormal behavior and, often, to impairment or loss of consciousness. Many antiepileptic drugs are available but seizures are poorly controlled in approx. one third of patients thus producing a socioeconomic impact as great as that of stroke or Parkinson. It is therefore crucial to understand the mechanisms involved in seizure initiation to develop more effective, mechanism-targeted therapeutic interventions. The objective of my studies is to identify how a seizure begins. To this end, I will use an established animal model of temporal lobe epilepsy in which we have discovered that progression to seizure activity is characterized in the EEG by increased occurrence of two specific types of high frequency oscillations, termed ripples and fast ripples. Since ripples and fast ripples may reflect the activation of distinctive neuronal networks we postulate that transition to seizures rests on two main mechanisms that will be firmly identified. We expect our future studies to clarify some of the contradictory findings regarding seizure initiation thus leading to specific pharmacological treatments.