Reward contingency gates selective cholinergic suppression of amygdala neurons

Abstract

SummaryBasal forebrain cholinergic neurons are thought to modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, memory, and motivated behavior. We questioned whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of ancillary roles in stimulus processing. We found that cholinergic neurons are active during behavioral responding for a reward – even in the absence of reward or discrete stimuli. Photostimulation of cholinergic neurons in the basal forebrain or their terminals in the basolateral amygdala (BLA) selectively drove conditioned responding (licking), but not unconditioned licking nor innate motor outputs. In vivo electrophysiological recordings revealed reward-contingency-dependent-gating of cholinergic suppression of BLA neural activity during cholinergic photostimulation, but not dorsomedial prefrontal cortex (dmPFC). Finally, cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic receptor signaling and facilitation of firing in GABAergic interneurons. Taken together, we show that cholinergic effects are modulated by reward contingency in a target-specific manner to promote conditioned responding. Given that the effects cholinergic photostimulation were modulated by rewards, our results constrain clinical goals of augmenting cholinergic function to improve neuropsychiatric symptoms.