We will use electrophysiological and in vivo electrochemical techniques to characterize acute neuronal responses to ethanol as direct membrane effects, modulatory interactions with synaptic inputs, or alterations in the activity of neuronal pathways. The effects of ethanol exposure on mammalian central nervous system function will be pursued using both extracellular recording of action potential activity from single neurons as well as evoked potentials, and intracellular recording of membrane properties. We will study ethanol effects in rodent brain using in vivo recording from intact brain in situ and in multiple brain grafts in oculo, and using brain slices and extricated intraocular brain grafts in vitro. We will also study ethanol actions on human neurons using in oculo brain xenografts. Finally, we will focus on genetic variants manifesting differential alcohol-related behavior as model systems for examining acute ethanol actions, ethanol dependence and ethanol withdrawal. New directions which I anticipate that these scientific interactions may take in my laboratory include studies of the neuronal effects of ethanol associated with fetal ethanol syndrome, the effect of ethanol on aging processes, the cellular mechanisms and genetics of ethanol involved in preference and dependence, studies of the role of growth factors in long-term effects of ethanol, and patch-clamp studies of the intracellular mechanisms, such as second messenger systems, mediating the effects of ethanol.