The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Nucleus Accumbens Medium Spiny Neuron Subtypes Mediate Depression-Related Outcomes to Social Defeat Stress
Open accessAbstract
Background The nucleus accumbens is a critical mediator of depression-related outcomes to social defeat stress. Previous studies demonstrate distinct neuroplasticity adaptations in the two medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 versus dopamine receptor D2, in reward and reinforcement leading to opposing roles for these MSNs in these behaviors. However, the distinct roles of nucleus accumbens MSN subtypes, in depression, remain poorly understood.Methods Using whole-cell patch clamp electrophysiology, we examined excitatory input to MSN subtypes and intrinsic excitability measures in D1-green fluorescent protein and D2-green fluorescent protein bacterial artificial chromosome transgenic mice that underwent chronic social defeat stress (CSDS). Optogenetic and pharmacogenetic approaches were used to bidirectionally alter firing of D1-MSNs or D2-MSNs after CSDS or before a subthreshold social defeat stress in D1-Cre or D2-Cre bacterial artificial chromosome transgenic mice.Results We demonstrate that the frequency of excitatory synaptic input is decreased in D1-MSNs and increased in D2-MSNs in mice displaying depression-like behaviors after CSDS. Enhancing activity in D1-MSNs results in resilient behavioral outcomes, while inhibition of these MSNs induces depression-like outcomes after CSDS. Bidirectional modulation of D2-MSNs does not alter behavioral responses to CSDS; however, repeated activation of D2-MSNs in stress naïve mice induces social avoidance following subthreshold social defeat stress.Conclusions Our studies uncover novel functions of MSN subtypes in depression-like outcomes. Notably, bidirectional alteration of D1-MSN activity promotes opposite behavioral outcomes to chronic social stress. Therefore, targeting D1-MSN activity may provide novel treatment strategies for depression or other affective disorders.
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“Nevertheless, activity in D1 MSNs is more likely to be associated with motivation, reward, and positive responses [193,[223][224][225] and resilience to stress [226].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [226]
In the citing paper
“Susceptibility to chronic social defeat stress is accompanied by atrophy of MSN dendrites, specifically in D1 MSNs and not D2 MSNs, and a corresponding loss of dendritic spines [226,234,235].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [226]
In the citing paper
“Susceptibility to chronic social defeat stress is accompanied by atrophy of MSN dendrites, specifically in D1 MSNs and not D2 MSNs, and a corresponding loss of dendritic spines [226,234,235].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [226]
In the citing paper
“Susceptibility to social defeat stress is accompanied by an increase in input resistance and firing in response to depolarizing currents pulses in D1 MSNs, but not D2 MSNs [226,234].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [226]
In the citing paper
“We recently found D1-MSNs display reduced mEPSC frequency and D2-MSNs display enhanced frequency of mEPSCs in CSDS susceptible mice (41).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“Like DBS, repeated high frequency stimulation of all NAc neurons alleviated depression-like outcomes to CSDS.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“It is likely D1-MSNs mediate this effect as cell-type specific stimulation of D1-MSNs mimicked non-specific NAc neuronal stimulation (41).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“D2-MSN stimulation promotes depressive-like outcomes (41), suggesting an imbalance in firing of MSN subtypes could mediate these symptoms.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“D2-MSN stimulation promotes depressive-like outcomes (41), suggesting an imbalance in firing of MSN subtypes could mediate these symptoms.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“Furthermore, repeated, but not acute stimulation is necessary for this behavioral effect.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“This interpretation would be consistent with observed excitatory changes on NAc MSN subtypes as well as stimulation-mediated antidepressant outcomes (41).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [41]
In the citing paper
“Thus, we believe the stress-related changes to spine density occur on D2-MSNs, as D2-MSNs do not undergo dendritic atrophy but have enhanced excitatory input [82].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [82]
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Citations
Cites
The functional anatomy of basal ganglia disorders
Albin, R. L., Young, A. B., & Penney, J. B. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90074-x · Cited by 5,353
D 1 and D 2 Dopamine Receptor-regulated Gene Expression of Striatonigral and Striatopallidal Neurons
Gerfen, C. R., Engber, T. M., Mahan, L. C., Susel, Z., Chase, T. N., Monsma, F. J., & Sibley, D. R. (1990) · Science · doi:10.1126/science.2147780 · Cited by 2,967
Krishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307 · cited 5×
“This is a well-established protocol that yields stress susceptible (mice displaying depression-like behaviors) or resilient cohorts (1,2,41).”
InfluentialEssential role of BDNF in the mesolimbic dopamine pathway in social defeat stress
Berton, O., McClung, C. A., DiLeone, R. J., Krishnan, V., Renthal, W., Russo, S. J., Graham, D., Tsankova, N. M., Bolanos, C. A., Rios, M., et al. (2006) · Science · doi:10.1126/science.1120972 · Cited by 2,129
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108
Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., & Roth, B. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700293104 · Cited by 2,046
Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C. (2010) · Nature · doi:10.1038/nature09159 · Cited by 1,885
Self-citationThe brain reward circuitry in mood disorders
Russo, S. J., & Nestler, E. J. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3381 · Cited by 1,870
A standardized protocol for repeated social defeat stress in mice
Golden, S. A., Covington, H. E., Berton, O., & Russo, S. J. (2011) · Nature Protocols · doi:10.1038/nprot.2011.361 · Cited by 1,581
The neostriatal mosaic: multiple levels of compartmental organization
Gerfen, C. R. (1992) · Trends in Neurosciences · doi:10.1016/0166-2236(92)90355-c · Cited by 1,471
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Bagot, R. C., Parise, E. M., Peña, C. J., Zhang, H.-X., Maze, I., Chaudhury, D., Persaud, B., Cachope, R., Bolaños-Guzmán, C. A., Cheer, J. F., et al. (2015) · Nature Communications · doi:10.1038/ncomms8062 · Cited by 491
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Metadata
- Authors
- Francis, T. C., Chandra, R., Friend, D. M., Finkel, E., Dayrit, G., Miranda, J., Brooks, J. M., Iñiguez, S. D., O’Donnell, P., Kravitz, A., & Lobo, M. K.
- Affiliations
- University of Maryland, Baltimore (US)
- National Institutes of Health (US)
- California State University, San Bernardino (US)
- Corresponding author
- Lobo, Mary Kay
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 77
- Issue
- 3
- Pages
- 212-222
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC5534173
- OpenAlex
- W2141609201
- Cited by
- 379
- References
- 60
- Citations by year
- 2026: 29 · 2025: 28 · 2024: 38 · 2023: 37 · 2022: 36 · 2021: 44 · 2020: 35 · 2019: 41 · 2018: 30 · 2017: 17 · 2016: 21 · 2015: 19
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH106500)
- National Institute of General Medical Sciences (T34GM083883, SC2GM109811)
- 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
- nucleus accumbens, medium spiny neurons, dopamine D1 receptor, dopamine D2 receptor, chronic social defeat stress, depression-like behavior, excitatory synaptic input, intrinsic excitability, social avoidance, neuronal activity modulation, depression resilience
- MeSH terms
- Action Potentials, Animals, Depressive Disorder, Dominance-Subordination, Male, Mice, Inbred C57BL, Mice, Transgenic, Nucleus Accumbens, Social Behavior, Stress, Psychological, Receptors, Dopamine D1, Receptors, Dopamine D2, Patch-Clamp Techniques, Tissue Culture Techniques, Resilience, Psychological, GABAergic Neurons, Anhedonia, Optogenetics
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