Cholinergic Interneurons Control Local Circuit Activity and Cocaine Conditioning
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Few But Powerful: Drug activation of the different types of acetylcholine receptors in cholinergic neurons often generates opposing or conflicting effects. Using optogenetic techniques in transgenic mice, Witten et al. (p. 1677 ) investigated the function of a rather enigmatic subpopulation of cholinergic neurons, the giant interneurons of the nucleus accumbens. Their excitation paradoxically reduced neighboring medium spiny neuron firing, while their inhibition increased medium spiny neuron firing. Furthermore, the giant interneurons were directly activated by cocaine, and silencing their drug-induced activity during cocaine exposure in freely behaving animals disrupted cocaine reward.
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Optogenetic inhibition of ChI enhances MSN spiking.
“Decreased ChI activity may modulate local MSN activity to cause depressive behaviors, as optogenetic inhibition of ChI enhances MSN spiking [159].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [159]
Decreased ChI activity may modulate local MSN activity to cause depressive behaviors.
“Decreased ChI activity may modulate local MSN activity to cause depressive behaviors, as optogenetic inhibition of ChI enhances MSN spiking [159].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [159]
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Self-citation
- Authors
- Witten, I. B., Lin, S.-C., Brodsky, M., Prakash, R., Diester, I., Anikeeva, P., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Witten, Ilana B.
- Lin, Shih-Chun
- Brodsky, Matthew
- Prakash, Rohit
- Deisseroth, Karl
- ORCID
- Venue
- Science
- Published
- 2010-12-17
- Volume
- 330
- Issue
- 6011
- Pages
- 1677-1681
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3142356
- OpenAlex
- W1966698116
- Cited by
- 467
- References
- 40
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 14 · 2023: 16 · 2022: 22 · 2021: 25 · 2020: 26 · 2019: 27 · 2018: 21 · 2017: 39 · 2016: 35 · 2015: 38 · 2014: 41 · 2013: 48 · 2012: 50
- FWCI
- 17.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (DP1OD000616)
- National Institute of Mental Health (R01MH075957, R01MH086373)
- National Institute on Drug Abuse (R01DA020794)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- cholinergic interneurons, nucleus accumbens, acetylcholine, optogenetic manipulation
- MeSH terms
- Acetylcholine, Action Potentials, Animals, Behavior, Animal, Choline O-Acetyltransferase, Cocaine, Conditioning, Psychological, Interneurons, Mice, Transgenic, Motor Activity, Neurons, Nucleus Accumbens, Reward, Mice, Inhibitory Postsynaptic Potentials, Synaptic Potentials
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