Cholinergic interneurons and dopamine in the nucleus accumbens

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  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.