The mammalian hippocampus is particularly sensitive to ethanol. Both clinical and basic studies have documented the neurophysiological and attendant neuropathological sequelae of excessive ethanol use on this brain structure. Moreover, cognitive deficits, including impairment in the consolidation of memory for recent events, have been documented in human alcohol abusers. Recent clinical evidence has demonstrated that anoxic lesions of particular hippocampal cell fields also leads to comparable cognitive impairment. These data reinforce a wealth of experimental data implicating this brain structure in information processing. The hippocampus is also capable of demonstrating unique short and long-term response """"""""plasticity"""""""" following repetitive stimulation of specific extrinsic and intrinsic inputs. The synaptic plasticity observed in these pathways has been hypothesized to be a neurophysiological substrate and cellular model for associative learning and memory. Although some hippocampal evoked events have been found to be compromised following chronic ethanol exposure, the effect of acute administration of ethanol on these processes remains to be investigated in the intact preparation. This is surprising given the increasing evidence that acute exposure to ethanol in human subjects may lead to transient cognitive deficits assessed by both electrophysiological and neuropsychological probes. The studies proposed in the present application will specifically focus on the effect of acute, intoxicating, doses of ethanol on these well described hippocampal mechanisms of synaptic plasticity. This research plan will seek to determine the sensitivity and time course of acute intoxicating doses of ethanol on hippocampal evoked synaptic activity. A broad spectrum of extracellular """"""""field potential"""""""" synaptic events will be studied including: 1. Primary cellular responsiveness; 2. Paired-pulse potentiation and inhibition; 3. Frequency potentiation/inhibition, and; 4. Long- term potentiation. In addition, potential neurochemical mediators of ethanol's effects will be evaluated. Three distinct hippocampal regions will be studied in order to determine potential regional selectivity for ethanol's action. This program of investigation will fill an important gap in the existing knowledge concerning the action of acute intoxicating doses of ethanol in a brain structure known to be sensitive to its action, and will provide a valuable comparison between the effects of acute and chronic ethanol exposure on synaptic plasticity in the hippocampus.
