Accumbens cholinergic interneurons dynamically promote dopamine release and enable motivation

Area of Science:

• Neuroscience
• Behavioral Neuroscience

Background:

• Dopamine (DA) in the nucleus accumbens (NAc) is essential for motivation.
• DA release in NAc is modulated by VTA neuron firing and local cholinergic interneurons (CINs).
• The role of CINs in NAc DA dynamics during behavior remains unclear.

Purpose of the Study:

• To investigate how CIN activity influences NAc DA release in awake, behaving rats.
• To understand the contribution of local CIN-driven DA release to motivated behaviors.

Main Methods:

• Monitoring DA release in the NAc Core using the RdLight1 sensor in awake rats.
• Simultaneously monitoring or manipulating CIN activity.
• Administering DHβE, a β2* nicotinic receptor antagonist, into the NAc.

Main Results:

• CIN stimulation evoked rapid NAc DA release without short-term depression.
• Food delivery cues and approach behaviors were associated with joint increases in CIN activity and DA release.
• DHβE administration impaired motivated approach decisions, similar to DA antagonists.
• CIN-driven DA release occurred independently of VTA DA neuron firing.

Conclusions:

• CINs play a critical role in regulating NAc DA release locally.
• This local DA modulation by CINs significantly influences motivated behaviors and decision-making.
• CINs provide a distinct pathway for controlling motivated behavior through nucleus accumbens dopamine.