The hypothesis for the proposed studies is that phosphorylation of the brain nicotinic receptor by protein kinase C (PKC) regulates the function of this receptor. The specific studies will assess the effects of PKC modulators on the rate of desensitization of the receptor, the extent of desensitization and recovery from desensitization. These studies will include the use of a strain of mice in which the PKC gamma isoform has been knocked out. This will allow examination of the role of the PKC gamma isoform in the regulation of neuronal nicotinic receptor function. The information gained from these studies should enhance our understanding of the regulation of brain nicotinic receptor function and could facilitate the development of new strategies that would be useful to help people stop smoking.