Cholinergic Interneurons Use Orbitofrontal Input to Track Beliefs about Current State

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• Organisms must adapt learning to changing environments without forgetting prior knowledge.
• Cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) are crucial for this state-dependent learning but their mechanism is unknown.

Purpose of the Study:

• Investigate the mechanism by which DMS CINs enable state-dependent learning.
• Determine if DMS CINs represent the current environmental state.

Main Methods:

• Recorded activity of putative CINs in the DMS of rats during a task with distinct trial blocks (states).
• Analyzed CIN ensemble activity in relation to behavioral choices and orbitofrontal cortex (OFC) input.

Main Results:

• Individual DMS CINs represented the current state throughout trials.
• DMS CINs, but not dorsolateral striatal CINs, tracked rats' beliefs about the current state.
• State representation in DMS CINs depended on OFC input and influenced rat choices.

Conclusions:

• DMS CINs maintain a real-time representation of the current environmental state.
• This function of CINs is essential for behavioral flexibility and state-dependent associative recall.
• Dysfunction in this mechanism may underlie generalization deficits in psychiatric disorders like addiction and anxiety.