Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior.
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 the serotonin 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.
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA. jschmidt@rockefeller.edu
Jennifer L
JL
Warner-Schmidt
Eric F
EF
Schmidt
John J
JJ
Marshall
Amanda J
AJ
Rubin
Margarita
M
Arango-Lievano
Michael G
MG
Kaplitt
Ines
I
Ibañez-Tallon
Nathaniel
N
Heintz
Paul
P
Greengard
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism*; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism*; D000099248:S100 Calcium Binding Protein A10
D000109:Acetylcholine; D017306:Annexin A2; D000928:Antidepressive Agents; D018832:Molecular Chaperones; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10