Cited by 1,073Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionStress Responses and Cortisol

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Dopamine neurons modulate neural encoding and expression of depression-related behaviour

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Tye, Kay M., Mirzabekov, Julie J., Warden, Melissa R., Ferenczi, Emily A., Tsai, Hsing-Chen, Finkelstein, Joel, Kim, Sung-Yon, Adhikari, Avishek, Thompson, Kimberly R., Andalman, Aaron S., Gunaydin, Lisa A., Witten, Ilana B., Deisseroth, Karl·2013·Nature

DOI 10.1038/nature11740PMC PMC4160519

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Abstract

Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.

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Retracted
The Effect of Maternal Methyl-Enriched Diet on the Number of Dopaminergic Neurons in the Ventral Tegmental Area in Adult Offspring of WAG/Rij Rats
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Authors: Tye, K. M., Mirzabekov, J. J., Warden, M. R., Ferenczi, E. A., Tsai, H.-C., Finkelstein, J., Kim, S.-Y., Adhikari, A., Thompson, K. R., Andalman, A. S., Gunaydin, L. A., Witten, I. B., & Deisseroth, K.
Affiliations: Massachusetts Institute of Technology (US)
Stanford University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Tye, Kay M.
Deisseroth, Karl
ORCID: Tye, Kay M.
Mirzabekov, Julie J.
Warden, Melissa R.
Tsai, Hsing-Chen
Finkelstein, Joel
Kim, Sung-Yon
Adhikari, Avishek
Gunaydin, Lisa A.
Witten, Ilana B.
Deisseroth, Karl
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-12-12
Volume: 493
Issue: 7433
Pages: 537-541
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11740
PMC: PMC4160519
OpenAlex: W2117782909
Cited by: 1,073
References: 34
Citations by year: 2026: 47 · 2025: 79 · 2024: 75 · 2023: 78 · 2022: 87 · 2021: 112 · 2020: 67 · 2019: 98 · 2018: 84 · 2017: 68 · 2016: 72 · 2015: 83 · 2014: 70 · 2013: 50 · 2012: 2
FWCI: 27.01
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
PMC
Funders: Howard Hughes Medical Institute
W. M. Keck Foundation
McKnight Foundation
National Alliance for Research on Schizophrenia and Depression
Defense Advanced Research Projects Agency
National Institute of Mental Health (F32 MH880102)
National Institute on Drug Abuse (DP2DA035149)
National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: midbrain dopaminergic neurons, ventral tegmental area, depression, chronic mild stress, social defeat, nucleus accumbens, neural coding, phasic neuronal activity, optogenetic manipulation, stress resilience, anhedonia, depression-like behavior, freely moving rodents
MeSH terms: Animals, Depression, Dopamine, Female, Male, Models, Neurological, Nucleus Accumbens, Phenotype, Stress, Psychological, Time Factors, Ventral Tegmental Area, Rats, Long-Evans, Mice, Rats, Dopaminergic Neurons, Optogenetics

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