Most Ventral Pallidal Cholinergic Neurons Are Bursting Basal Forebrain Cholinergic Neurons with Mesocorticolimbic...

The ventral pallidum (VP) lies at the intersection of basal ganglia and basal forebrain circuitry, possessing attributes of both major subcortical systems. Basal forebrain cholinergic neurons (BFCNs) are rapidly recruited by reinforcement feedback and project to cortical and subcortical forebrain targets; in contrast, striatal cholinergic cells are local interneurons exhibiting classical "pause-burst" responses to rewards. However, VP cholinergic neurons (VPCNs) are less characterized, and it is unclear whether basal forebrain and striatal-type cholinergic neurons mix in the VP. Therefore, we performed anterograde and monotranssynaptic retrograde labeling, in vitro acute slice recordings and bulk calcium recordings of VPCNs in mice of either sex. We found that VPCNs broadly interact with the mesocorticolimbic circuit that processes rewards and punishments, targeting the basolateral amygdala, the medial prefrontal cortex, and the lateral habenula while receiving inputs from the nucleus accumbens, hypothalamus, central amygdala, bed nucleus of stria terminalis, and ventral tegmental area. Bulk calcium recordings revealed that VPCNs responded to rewards, punishments, and reward-predicting cues. Acute slice recordings showed that most VPCNs resembled the bursting type of BFCNs, while a few of them were of the regular rhythmic type, which differentiated most VPCNs from striatal cholinergic interneurons. These results were confirmed by in vivo electrophysiological recordings of putative VPCNs. We conclude that VPCNs show burst firing and specialized connectivity to relay aversive and appetitive stimuli to the reinforcement circuitry, possibly implicated in mood disorders and addiction.