Stress and cocaine trigger divergent and cell type-specific regulation of synaptic transmission at single spines in nucleus accumbens
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Background Repeated exposure to cocaine or social stress leads to lasting structural and functional synaptic alterations in medium spiny neurons (MSNs) of nucleus accumbens (NAc). Although cocaine-induced and stress-induced structural changes in dendritic spines have been well documented, few studies have investigated functional consequences of cocaine and stress at the level of single spines.Methods We exposed mice to chronic cocaine or chronic social defeat stress and used two-photon laser scanning microscopy with glutamate photo-uncaging and whole-cell recording to examine synaptic strength at individual spines on two distinct types of NAc MSNs in acute slices after 24 hours of cocaine withdrawal and after chronic social defeat stress.Results In animals treated with cocaine, average synaptic strength was reduced specifically at large mushroom spines of MSNs expressing dopamine receptor type 1 (D1-MSNs). In contrast, cocaine promoted a rightward shift in the distribution of synaptic weights toward larger synaptic responses in MSNs expressing dopamine receptor type 2 (D2-MSNs). After chronic social defeat stress, resilient animals displayed an upregulation of synaptic strength at large mushroom spines of D1-MSNs and a concomitant downregulation in D2-MSNs. Although susceptible mice did not exhibit a significant overall change in synaptic strength on D1-MSNs or D2-MSNs, we observed a slight leftward shift in cumulative distribution of large synaptic responses in both cell types.Conclusions This study provides the first functional cell type-specific and spine type-specific comparison of synaptic strength at a single spine level between cocaine-induced and stress-induced neuroadaptations and demonstrates that psychoactive drugs and stress trigger divergent changes in synaptic function in NAc.
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Resilient mice display opposing adaptive mechanisms at individual medium spiny neuron subtypes.
“While the results suggest resilient mice display opposing adaptive mechanisms at single MSN subtypes, more holistic studies are needed to analyze cell-type specific synaptic changes as they are related to morphological changes and cellular output.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [40]
In nucleus accumbens shell, D1 medium spiny neuron mushroom spines from resilient animals show enhanced synaptic strength, while D2 medium spiny neuron mushroom spines show reduced strength.
“Cell-type specific analysis of NAc shell thin and mushroom spines display enhanced synaptic strength of D1-MSN mushroom spines from resilient animals and reduced strength of D2-MSN mushroom spines (40).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [40]
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- Authors
- Khibnik, L. A., Beaumont, M., Doyle, M., Heshmati, M., Slesinger, P. A., Nestler, E. J., & Russo, S. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Russo, Scott J.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 79
- Issue
- 11
- Pages
- 898-905
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4670821
- OpenAlex
- W585546046
- Cited by
- 67
- References
- 52
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 1
- FWCI
- 4.49
- 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
- US National Institutes of Health Grants (R01 MH090264, R01 MH104559, R01 DA014133, R01 MH051399)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- cocaine, social defeat stress, nucleus accumbens, medium spiny neurons, dendritic spines, synaptic efficacy, mushroom spines, dopamine D1 receptor, dopamine D2 receptor, cocaine withdrawal, neural adaptation, synaptic plasticity
- MeSH terms
- Animals, Cocaine, Dominance-Subordination, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Nucleus Accumbens, Stress, Psychological, Substance Withdrawal Syndrome, Receptors, Dopamine D1, Receptors, Dopamine D2, Patch-Clamp Techniques, Microscopy, Confocal, Glutamic Acid, Dopamine Uptake Inhibitors, Excitatory Postsynaptic Potentials, Tissue Culture Techniques, Dendritic Spines, Green Fluorescent Proteins
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