However, the precise role that endogenous cholinergic activity exerts on DA release in the NAc has not been explored. Endogenous release of acetylcholine (ACh) obtained by optogenetic control of CINs allows for the elucidation of cholinergic receptor action when activation occurs by the natural ligand. To examine the effect of endogenously released ACh on terminal DA release we used a combination of optogenetic techniques for selective stimulation of CINs, combined with electrophysiology, real-time detection of DA levels and pharmacology. Activation of CINs is sufficient to evoke DA release in the NAc, independently of contingent activation of the VTA, in vitro and in vivo. We further reveal that endogenous cholinergic control of DA release is not only mediated by nAChRs and modulated by mAChRs, but also results from actions at AMPA receptors. Hence, our results show that endogenous cholinergic activity exerts a powerful influence on accumbal DA release and that this phenomenon recruits a previously unrecognized convergence of neurotransmitter systems.
