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Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning

Witten, Ilana B. and Lin, Shih-Chun and Brodsky, Matthew and Prakash, Rohit and Diester, Ilka and Anikeeva, Polina and Gradinaru, Viviana and Ramakrishnan, Charu and Deisseroth, Karl (2010) Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning. Science, 330 (6011). pp. 1677-1681. ISSN 0036-8075. PMCID PMC3142356.

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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.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Gradinaru, Viviana0000-0001-5868-348X
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.
Funding AgencyGrant Number
Helen Hay Whitney FoundationUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Deutscher Akademischer Austauschdienst (DAAD)UNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Stanford Dean’s FellowshipUNSPECIFIED
Stanford Interdisciplinary Graduate Fellowship ProgramUNSPECIFIED
McKnight FoundationUNSPECIFIED
California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
National Institute of Mental Health (NIMH)UNSPECIFIED
National Institute on Drug AbuseUNSPECIFIED
W. M. Keck FoundationUNSPECIFIED
H. L. Snyder Medical FoundationUNSPECIFIED
Albert Yu and Mary Bechmann FoundationUNSPECIFIED
Issue or Number:6011
PubMed Central ID:PMC3142356
Record Number:CaltechAUTHORS:20121211-085000915
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35901
Deposited By: Tony Diaz
Deposited On:12 Dec 2012 22:43
Last Modified:03 Oct 2019 04:32

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