The proposed studies will examined the temporal discharge properties of single cerebellar neurons at low (0-1 gm/kg), medium (1-2 gm/kg), and high (3-4 gm/kg) doses of ethanol. This information, together with the neuron's sensitivity toward ethanol, will be utilized to evaluate the role of reverberation from recurrent feedback loops in the formation of patches of ethanol-sensitive and ethanol-resistant cells. Anatomical substrates underlying the differential sensitivity shall be investigated by correlating the topographical distribution of cells displaying characteristic temporal discharge patterns with the topographic distribution of feedback collaterals from Purkinje cells. An important additional objective is to determine the correlation between cellular sensitivity to ethanol with the development of tolerance. Dose-response relationships will be monitored to document the onset as well as the kinetics of development of tolerance for single neurons in the cerebellum. These studies shall be carried out using the cat as a model. The overall objective is to determine the synaptic mechanisms involved in the loss of cerebellar function and the development of tolerance as a result of ethanol. This knowledge should be important to the understanding of intoxication, tolerance, and dependence due to alcohol abuse.
