Publication Date:
2010-12-18
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142356/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142356/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witten, Ilana B -- Lin, Shih-Chun -- Brodsky, Matthew -- Prakash, Rohit -- Diester, Ilka -- Anikeeva, Polina -- Gradinaru, Viviana -- Ramakrishnan, Charu -- Deisseroth, Karl -- DP1 OD000616/OD/NIH HHS/ -- DP1 OD000616-01/OD/NIH HHS/ -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 DA020794-01/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH075957-01A2/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- R01 MH086373-01/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1677-81. doi: 10.1126/science.1193771.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164015" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylcholine/*physiology
;
Action Potentials
;
Animals
;
Behavior, Animal
;
Choline O-Acetyltransferase/genetics/metabolism
;
Cocaine/administration & dosage/*pharmacology
;
*Conditioning (Psychology)
;
Inhibitory Postsynaptic Potentials
;
Interneurons/drug effects/*physiology
;
Mice
;
Mice, Transgenic
;
Motor Activity/drug effects
;
Neurons/drug effects/*physiology
;
Nucleus Accumbens/cytology/drug effects/*physiology
;
Reward
;
Synaptic Potentials
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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