INFERIOR COLLICULUS CALCIUM CURRENT AND SEIZURE

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Epilepsies are disorders of neuronal excitability. At the cellular level, seizure activity consists of trains of depolarizing voltage shifts (DS) which requires calcium (Ca) influx. The long-term objectives of this project are to identify the cellular and molecular changes in proteins underlying seizure activity. The aim of this proposal is to characterize which aspects of Ca currents have been changed after ethanol withdrawal (ETX), and audiogenic seizure (AGS) following ETX, a model of generalized epilepsy. The specific aims of this research proposal are 1)to pharmacologically and biophysically identify the types of Ca currents in acutely dissociated inferior colliculus (IC) neurons using patch-clamp techniques, 2) to characterize the effects of voltage on N- and L-type Ca channel activity in IC neurons 3) to examine the effects of ETX episode, and AGS on Ca currents 4) to identify which Ca channel subunit are expressed in the IC using molecular techniques 4) to determine if ETX and/or AGS alter Ca subunit mRNA levels. Determining a role for Ca influx in the mechanism of ETX seizure in the IC may be relevant to clinical generalized seizure with tonic-clonic motor behaviors. Understanding the cellular and molecular basis of epilepsy will improve therapeutic strategies as well as yield new insights into brain function and structure.