Acute and chronic effects of ethanol on synaptic transmission are critically involved in the effects and neuropathologies such as induction and expression of severe alcohol-related intoxication, neurotoxicity, dependence and withdrawal. Evidence suggests that such effects of ethanol are at least in part dependent upon modification of information processing at the level of the synapse. Primary sites of ethanol action at the synaptic level include glutamate receptors and voltage-gated calcium channels (VGCCs). Recent evidence suggests complex roles for VGCCs in both presynaptic and postsynaptic components of glutamatergic synaptic transmission. preliminary data from this laboratory demonstrates ethanol modulation of both of these presynaptic and postsynaptic VGCC-mediated effects. We propose to investigate these interactions through the use of patch clamp recording of spontaneously-occurring synaptic events (mEPSCs) mediated by glutamate receptor activation (GLU) in brain slice preparations. Frequency and amplitude comparisons will be used to assess presynaptic and postsynaptic components of synaptic transmission. Initially, these studies will assess acute effects of ethanol on basal mEPSCs recorded under controlled conditions. Second, ethanol effects on mEPSCs enhanced by specific and selective measures to modify the involvement of presynaptic and postsynaptic VGCCs in glutamatergic transmission will be analyzed. Third, the modulation of these processes by chronic ethanol exposure in hippocampal explant cultures will be assessed. Finally, quantitative autoradiographic techniques will be used to measure subtypes of VGCCs following acute and chronic treatments. Taken together, such information will increase our understanding of the effects of ethanol at the synaptic level and also help define short and long-term synaptic alterations related too the development and expression of various neuropathologic effects of alcohol.
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