ONTOGENY OF SEIZURE SUPPRESSION

Epidemiologic studies indicate that seizure disorders are more frequent early in life. The objective of this international collaboration is to identify the mechanisms involved in the suppression of seizures as a function of age. Ongoing studies in the parent grant using the flurothyl seizure model suggest that the increased seizure susceptibility of the immature brain may be due to age-specific differences in the GABA(A) receptor subtype within the substantia nigra, a site that is crucial for the control of seizures in adults. This proposal takes advantage of the expertise of the principal investigator and Dr. Mares, two pioneers in the field of developmental epilepsy, and foster close international collaboration between the two laboratories. The aim is to determine whether the ontogenetic influence of the substantia nigra on seizures depends on the model used to induce seizures. Methods include intracranial localized microinfusions, systemic infusions of chemoconvulsants, behavioral observations and EEG recordings. Rats of various ages will be used to determine the maturational profile of the substantia nigra-mediated seizure modification in the bicuculline and N- methyl-D-aspartate model of epilepsy. These studies may lead to the development of new therapeutic treatments that will compensate for the maturational state of the CNS.