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Related Experiment Video

Updated: May 21, 2026

Animal Models of Depression - Chronic Despair Model (CDM)

Animal Models of Depression - Chronic Despair Model (CDM)

Published on: September 23, 2021

Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior.

Jennifer L Warner-Schmidt¹, Eric F Schmidt, John J Marshall

¹Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA. jschmidt@rockefeller.edu

Proceedings of the National Academy of Sciences of the United States of America

|June 27, 2012

Summary

Researchers identified cholinergic interneurons (CINs) in the nucleus accumbens (NAC) as key players in mood regulation. Decreased p11 levels in these neurons cause depression-like behaviors in mice.

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Area of Science:

Neuroscience
Molecular Biology
Psychiatry

Background:

The nucleus accumbens (NAC) is vital for reward, motivation, and mood.
Neuronal cell types regulating these processes, especially in depression, remain unidentified.
The serotonin receptor chaperone p11 is implicated in depression-like states.

Purpose of the Study:

To identify specific neuronal cell types in the NAC involved in mood regulation.
To elucidate the role of p11 in the NAC's function related to depression.
To understand the biological basis of mood and major depressive disorder.

Main Methods:

Investigated the role of p11 in the NAC.
Focused on cholinergic interneurons (CINs) within the NAC.
Reduced p11 levels in NAC CINs of mice.
Silenced neuronal transmission in NAC CINs.

Main Results:

Cholinergic interneurons (CINs) in the NAC are identified as a primary site of p11 action.
Decreased p11 levels in NAC CINs led to depression-like behavior in mice.
Silencing neuronal transmission in these CINs replicated the depression-like phenotype.

Conclusions:

Accumbal cholinergic neuronal activity regulates depression-like behaviors.
Activity of accumbal CINs is crucial for mood and motivation regulation.
p11 in NAC CINs is a key molecular regulator of depression-like states.