Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior

Jennifer L. Warner-Schmidt*, Eric F. Schmidt, John J. Marshall, Amanda J. Rubin, Margarita Arango-Lievano, Michael G. Kaplitt, Ines Ibañez-Tallon, Nathaniel Heintz, Paul Greengard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


A large number of studies have demonstrated that the nucleus accumbens (NAC) is a critical site in the neuronal circuits controlling reward responses, motivation, and mood, but the neuronal cell type(s) underlying these processes are not yet known. Identification of the neuronal cell types that regulate depression-like states will guide us in understanding the biological basis of mood and its regulation by diseases like major depressive disorder. Taking advantage of recent findings demonstrating that theserotonin receptor chaperone, p11, is an important molecular regulator of depression-like states, here we identify cholinergic interneurons (CINs) as a primary site of action for p11 in the NAC. Depression-like behavior is observed in mice after decrease of p11 levels in NAC CINs. This phenotype is recapitulated by silencing neuronal transmission in these cells, demonstrating that accumbal cholinergic neuronal activity regulates depression-like behaviors and suggesting that accumbal CIN activity is crucial for the regulation of mood and motivation.

Original languageEnglish (US)
Pages (from-to)11360-11365
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number28
StatePublished - Jul 10 2012


  • Acetylcholine
  • Antidepressant
  • Neurotransmission
  • S100a10

ASJC Scopus subject areas

  • General


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