Ethanol use leads to a variety of behavioral, cognitive and associative dysfunctions that can have adverse social consequences. The neural basis for ethanol's impairment of associative processes such as working memory are not well understood, but probably involve the hippocampus. The proposed project aims to determine the effect of ethanol on memory-related hippocampal neuronal activity and to explore the hypothesis that ethanol's memory-impairing effects involve disruption of information processing capabilities of the hippocampus. The experiments apply newly developed animal models that closely mimic cognitive processes tested in humans and a high capacity physiological data acquisition system. The simultaneous assessment of complex associative processes and hippocampal neuronal activity in this proposal represent a new approach for understanding the neural basis of the cognitive dysfunction associated with ethanol use. Based on preliminary data, hippocampal neurons in the rat are engaged in the memory components of the working memory task (eg., delay, sequence, accuracy). By establishing mnemonic correlates for a given animal during a baseline period, and then administering low doses of ethanol, the effect of ethanol on both memory and single unit activity can be simultaneously assess. Low doses of ethanol disrupt neural activity in the medial septal area (MSA) via a GABAergic mechanism. The MSA provides a major input to the hippocampus, and thus if disrupted could interfere with information processing in the hippocampal circuitry and impair working memory. This hypothesis is tested using direct microinfusion of drugs that act on the GABA-A receptor into the MSA in rats from which mnemonic correlates of hippocampal unit activity are recorded. The data from these studies will determine the interaction of the MSA with cognitive impairments of hippocampal function by ethanol.
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