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Published December 17, 2010 | Accepted Version + Supplemental Material
Journal Article Open

Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning


Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals.

Additional Information

© 2012 American Association for the Advancement of Science. Received for publication 15 June 2010. Accepted for publication 10 November 2010. We thank the entire Deisseroth lab for their support. I.B.W. is supported by the Helen Hay Whitney Foundation; S.-C.L. is supported by the National Institute of Neurological Disorders and Stroke; I.D. is supported by DAAD and the Human Frontier Science Program; P.A. is supported by the Stanford Dean's fellowship; V.G. is supported by Bio-X SIGF; K.D. is supported by the Keck, Snyder, Woo, Yu, and McKnight Foundations, as well as by CIRM, the National Institute of Mental Health, and the National Institute on Drug Abuse.

Attached Files

Accepted Version - nihms-308432.pdf

Supplemental Material - Witten.SOM.pdf


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