Variations in desensitization of nicotinic acetylcholine receptors from hippocampus and midbrain dopamine areas

This study addresses two issues arising from the desensitization of nicotinic acetylcholine receptors from the hippocampus, ventral tegmental area, and substantia nigra. First, biophysical studies can find potent and complete desensitization of nicotinic receptors; but in vivo studies often find that desensitization affecting a behavior is less than complete, or that desensitization is important over a different nicotine concentration range. Our results show that there can be significant differences in desensitization when comparing nearby neurons from the same area of the brain. Thus, nicotinic receptors on a minority of neurons may remain active and maintain a behavior under conditions that can produce significant desensitization. Second, agonist applications that are intended to active nicotinic receptors also cause desensitization. The prevailing conditions and the rate of agonist application and removal will control the degree of activation vs. desensitization. These and other factors regulate the efficacy of nicotinic agonists experimentally and physiologically.