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Cholinergic interneurons and dopamine in the nucleus accumbens

Mohebi, Ali1; Collins, Val2; Berke, Joshua2

Research facility: University of California, San Francisco
Published Aug 30, 2023 on Dryad. https://doi.org/10.7272/Q68P5XST

Data files

Aug 30, 2023 version files 214.51 MB

Abstract

Motivation to work for potential rewards is critically dependent on dopamine (DA) in the nucleus accumbens (NAc). DA release from NAc axons can be controlled by at least two distinct mechanisms: 1) action potentials propagating from DA cell bodies in the ventral tegmental area (VTA), and 2) activation of β2* nicotinic receptors by local cholinergic interneurons (CINs). How CIN activity contributes to NAc DA dynamics in behaving animals remains unclear. We monitored DA release in the NAc Core of awake, unrestrained rats while simultaneously monitoring or manipulating CIN activity at the same location. CIN stimulation rapidly evoked DA release, and in contrast to slice preparations, this DA release showed no indication of short-term depression or receptor desensitization. The sound of food delivery evoked a brief joint increase in CIN population activity and DA release, with a second joint increase as rats approached the food. In an operant task, we observed fast ramps in CIN activity during approach behaviors, either to start the trial or to collect rewards. These CIN ramps co-occurred with DA release ramps, without corresponding changes in the firing of VTA DA neurons. Finally, we examined the effects of blocking CIN influence over DA release through local NAc infusion of DHβE, a selective antagonist of Embedded Image nicotinic receptors. DHβE dose-dependently interfered with motivated approach decisions, mimicking the effects of a DA antagonist. Our results support a key influence of CINs over motivated behavior via the local regulation of DA release.