Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin
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Significance: Dopamine (DA) and serotonin (5-HT) release in the nucleus accumbens (NAc) influence motivated behaviors, yet the mechanisms by which they modulate NAc activity are unclear. Here, we report that DA selectively reduced excitatory postsynaptic currents (EPSCs) from paraventricular thalamus (PVT) inputs, whereas 5-HT reduced EPSCs from PVT, ventral hippocampus (vHip), and basolateral amygdala (BLA) inputs but not medial prefrontal cortex (mPFC) inputs. Mimicking the input-specific effect of DA via optogenetic inhibition of the PVT promoted cocaine-conditioned place preference, while inhibition of the mPFC blocked the enhancement of sociability induced by (±)3,4-methylenedioxymethamphetamine (MDMA). Together, these results suggest that these input-specific effects on NAc excitatory transmission contribute to the distinct modulation of behavior that is generated by release of DA and 5-HT.
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Inhibition of basolateral amygdala-to-nucleus accumbens inputs enhanced sociability, but inhibition of ventral hippocampus-to-nucleus accumbens inputs decreased sociability.
“Consistent with these findings, we found that inhibition of BLA-to-NAc inputs enhanced sociability but surprisingly observed a decrease in sociability when vHip-to-NAc inputs were optogenetically inhibited [65].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [65]
Bath application of dopamine or methamphetamine depressed responses generated by paraventricular thalamus inputs while having minimal effects on those generated by ventral hippocampus, basolateral amygdala, and medial prefrontal cortex inputs.
“In marked contrast, bath application of DA or methamphetamine (to release endogenous DA) depressed responses generated by PVT inputs while having minimal effects on those generated by the three other brain regions.”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [65]
Bath application of serotonin or MDMA depressed excitatory postsynaptic responses in D1 medium spiny neurons generated by ventral hippocampus, basolateral amygdala, and paraventricular thalamus inputs but spared those generated by medial prefrontal cortex inputs.
“Bath application of 5-HT or MDMA (to release endogenous 5-HT) depressed excitatory postsynaptic responses in D1 medium spiny neurons generated by vHip, BLA and PVT inputs but surprisingly spared those generated by mPFC inputs.”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [65]
Inhibition of either paraventricular thalamus-to-nucleus accumbens or medial prefrontal cortex-to-nucleus accumbens inputs did not alter sociability, although the latter manipulation prevented the enhanced sociability elicited by systemic MDMA administration.
“In contrast, inhibition of either PVTto-NAc or mPFC-to-NAc inputs did not alter sociability although the latter manipulation prevented the enhanced sociability elicited by systemic MDMA administration [65].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [65]
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Self-citation
- Authors
- Christoffel, D. J., Walsh, J. J., Hoerbelt, P., Heifets, B. D., Llorach, P., Lopez, R. C., Ramakrishnan, C., Deisseroth, K., & Malenka, R. C.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Malenka, Robert C.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-06-08
- Volume
- 118
- Issue
- 24
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8214692
- OpenAlex
- W3171015631
- Cited by
- 54
- References
- 64
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 10 · 2023: 7 · 2022: 8 · 2021: 3
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (F32 MH115668, K08 MH110610)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (K99 DK115895)
- HHS | NIH | National Institute on Drug Abuse (P50 DA042012)
- UCSF Dolby Family Center for Mood Disorders (NA)
- 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 › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- nucleus accumbens, dopamine, serotonin, excitatory synaptic transmission, medium spiny neurons, paraventricular thalamus, ventral hippocampus, basolateral amygdala, medial prefrontal cortex, methamphetamine, MDMA, cocaine conditioned place preference, sociability, motivated behavior
- MeSH terms
- Social Interaction, Animals, Behavior, Animal, Dopamine, Methamphetamine, Mice, Inbred C57BL, Synaptic Transmission, Neurons, Nucleus Accumbens, Serotonin, N-Methyl-3,4-methylenedioxyamphetamine, Excitatory Postsynaptic Potentials, Mice
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