Segregated cholinergic transmission in the ventral tegmental area

Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures associated with either movement or reward. While cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. Here we used optogenetic methods combined with in vivo juxtacellular recording and labeling to dissect the influence of brainstem cholinergic innervation of distinct subpopulations of neurons in the VTA. We found that LDT cholinergic axons selectively enhance the bursting activity of mesolimbic dopamine neurons that are excited by aversive stimulation. In contrast, PPN cholinergic axons activate and change the discharge properties of VTA neurons that are integrated in distinct functional circuits and are inhibited by aversive stimulation. While both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate neurons involved in different reward circuits.