Project III addresses clinical and experimetal challenges by using novel methodology to test this important molecular target. In a “personalized medicine” approach, only PD subjects demonstrated to have significant cholinergic degeneration (in Project II) will be studied. Novel PET methods are used to examine therapeutically relevant pharmacological features of α4β2* nAChR in these hypocholinergic subjects. We test the hypothesis that agonism of the α4β2* nAChR in PD improves laboratory measures of gait, postural control and attentional function. Related information comes from the comparison of α4β2* nAChR agonism in patients and the rodent model developed in Project I.