Studies of nAChR dynamics (desensitization or antagonism) have long suggested that endogenous cholinergic tone may establish the baseline for the probability of DA release modulates DA release in the striatum (Giorguieff et al., 1976; Zhou et al., 2001; Zhang and Sulzer, 2004; Threlfell et al., 2010). This phenomenon has a presynaptic locus of action, as studied by application of exogenous acetylcholine (ACh) or ligands of the nAChR in striatal synaptosomes (Rapier et al., 1990; Wonnacott et al., 2000; Chéramy et al., 1996) or slices (Giorguieff et al., 1977; Wonnacott et al., 2000). However, is not known whether selective activation of CINs and subsequent release of endogenous ACh can directly control DA release. To test this hypothesis, we utilized optogenetic techniques to selectively activate CINs in the NAc. Briefly, we injected an adeno-associated virus encoding channelrhodopsin2 (ChR2) and enhanced yellow fluorescent protein (eYFP) into the NAc of mice expressing Cre-recombinase downstream of the choline-acetyltransferase (ChAT) promoter (ChAT-Cre mice) (see Methods). Four weeks after viral injection, studies were performed in coronal slices of the NAc.
