Nucleus Accumbens Cholinergic Interneurons Oppose Cue-Motivated Behavior

Area of Science:

• Neuroscience
• Behavioral Science
• Neuropharmacology

Background:

• Reward-predictive cues motivate adaptive behavior, primarily mediated by the nucleus accumbens (NAc) core.
• Cholinergic interneurons within the NAc are well-positioned to modulate NAc function due to their activity and structure.
• The specific role of NAc cholinergic interneurons in adaptive behavior has remained unclear.

Purpose of the Study:

• To investigate the causal contribution of nucleus accumbens (NAc) cholinergic interneurons to cue-motivated behavior.
• To elucidate the function of NAc cholinergic interneurons in regulating adaptive reward pursuit.

Main Methods:

• Utilized chemogenetics and optogenetics to manipulate NAc cholinergic interneuron activity in rats.
• Employed pharmacology to investigate receptor involvement.
• Used a Pavlovian-to-instrumental transfer task to assess cue-motivated reward-seeking behavior.

Main Results:

• Activity of NAc cholinergic interneurons was found to oppose the motivating influence of appetitive cues.
• Inhibiting these interneurons using chemogenetics increased cue-motivated behavior.
• Stimulating acetylcholine release from these interneurons, via optogenetics, attenuated cue-induced behavioral invigoration, mediated by nicotinic acetylcholine receptors.

Conclusions:

• NAc cholinergic interneurons play a critical regulatory role in adaptive cue-motivated behavior.
• These findings identify NAc cholinergic interneurons as a potential therapeutic target for psychiatric conditions characterized by maladaptive cue-motivated behavior, such as addiction and depression.