Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior

Abstract

ABSTRACTBackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.MethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.ResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of β2-containing nicotinic acetylcholine receptors.ConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.