NEURONAL EXCITABILITY IN CHRONIC EPILEPTOGENESIS

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DESCRIPTION (provided by applicant): Electrophysiological and anatomical studies will be done on a rat model of post-traumatic epilepsy to address questions of alterations in excitatory and inhibitory mechanisms within the neocortex that might lead to epilepsy following injury. Epileptogenic lesions are produced in adult rats by making partial cortical isolations that generate abnormal discharges within 2-3 weeks. Studies are planned to assess alterations in GABA-A receptor-mediated inhibition that might be produced by changes in the chloride gradient of post-synaptic neurons, due to a down regulation of the K/Cl co-transporter, KCC2. Other experiments will assess the excitatory and inhibitory synaptic inputs to inhibitory interneurons within the epileptogenic cortex, to test the hypothesis that these cells receive less excitatory and/or more inhibitory functional innervation. In other experiments, connectivity within layer V of the abnormal cortex will be studied to determine whether axonal sprouting results in abnormal functional excitatory connectivity. Techniques employed will include immunocytochemistry, whole cell recordings of currents and potentials in cortical neurons, minimal stimulation and the application of scanning laser photolysis of caged glutamate. Results are relevant to the mechanisms of epilepsy that develop following brain trauma. The long-term goal is to use this information to find strategies that will prevent post-traumatic epilepsy.