Journal
SCIENCE
Volume 330, Issue 6011, Pages 1677-1681Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1193771
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Funding
- Deisseroth lab
- Helen Hay Whitney Foundation
- National Institute of Neurological Disorders and Stroke
- DAAD
- Human Frontier Science Program
- Stanford Dean's fellowship
- Bio-X SIGF
- Keck Foundation
- Snyder Foundation
- Woo Foundation
- Yu Foundation
- McKnight Foundation
- CIRM
- National Institute of Mental Health
- National Institute on Drug Abuse
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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.
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