ArticleBiological psychiatry2015
Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress.
Article in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers.
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Who cites it
232 citing papers in PubMed, 377 citations in OpenAlex.
- Early life experiences, the neural epigenome and affective disorder risk.Nature reviews. Neuroscience · 2026Review
- Nucleus accumbens neuron subtype translatome signatures in socially stressed females.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Distinct electrophysiology and dopaminergic modulation of medium spiny neurons across divisions of the tail striatum and the dorsolateral striatum.Experimental physiology · 2026Article
- Synaptic Actions of Estradiol in the Brain's Reward System: Linking Mechanisms to Behavior and Disease.Biological psychiatry global open science · 2026Review
- Altered Postnatal Chromatin Development in the Nucleus Accumbens Primes Enduring Stress Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Mitofusin-2 in ventral striatal D1 neurons regulates effort-based motivation through sex-specific mitochondrial-synaptic reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dual regulatory roles of CPT1C in chronic stress-induced depression-related outcomes.Molecular psychiatry · 2026Article
- Neural basis of social hierarchy across species.Nature reviews. Neuroscience · 2026Review
- Social Novelty Recruits a Dysfunctional Nucleus Accumbens Ensemble That Drives Social Avoidance in abioRxiv : the preprint server for biology · 2026Article
- Article
- MeCP2 regulates cell-type-specific functions of depressive-like symptoms in the nucleus accumbens.Experimental & molecular medicine · 2026Article
- Deep Brain Stimulation Induces Antidepressant Effects by Restoring High-Fidelity Communication in the BNST-NAc Circuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell Type-Specific Downregulation of Dnmt3a in Nucleus Accumbens Oligodendrocytes Prevents Myelin Damage and Reduces Susceptibility to Social Stress in Male Mice.Biomolecules · 2026Article
- Cue-Dependent Fear Learning Drives Nucleus Accumbens Spine Plasticity.bioRxiv : the preprint server for biology · 2026Article
- Review
- Adenosine A2A receptors in the nucleus accumbens regulate stress resilience and predict susceptibility to stress-induced affective disturbances.Purinergic signalling · 2026Article
- Neurobiology of resilience to early life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Nucleus accumbens DRD2 receptor agonism attenuates escape behavior.Frontiers in neuroscience · 2026Article
- Article
172 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe 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.
methodsUsing 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.
resultsWe 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.
conclusionsOur 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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