Project: Research project

Project Details


The objective of this proposal is to identify the mechanism
involved in the suppression of seizures as a function of age.
Ongoing studies have demonstrated that the increased seizure
susceptibility of the immature brain may be due to an alteration
of the functional activity of the GABA sensitive neurons in the
substantia nigra (SN) and their efferent connections. The aims of
the proposal are to determine: 1) the age-related differences in
the development of GABA receptor substypes in the SN; 2) the role
of specific GABA receptor subtypes in the SN-mediated modification
of seizures in adults and rat pups; 3) the efferent pathways from
the SN that mediate the different GABAergic effects on seizures in
adults and rat pups. The methods include in vivo
studies to determine the seizure susceptibility of adult rats
and 16-day old rat pups after GABAergic pre-treatment using
chronically implanted cannulae, intracranial microinfusions and the
flurothyl model of epilepsy; in vitro quantitative light microscopy
receptor autoradiography; and deoxyglucose autoradiographic studies
to map the SN efferent pathways. The goal is to develop a better
understanding of the endogenous processes involved in the
modification of seizures with maturation. These studies may lead
to the development of new therapeutic approaches that will
compensate for the maturational state of the CNS.
Effective start/end date12/31/898/31/13


  • Medicine(all)
  • Neuroscience(all)
  • Clinical Neurology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physiology


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