Serotonergic versus nonserotonergic dorsal raphe projection neurons: differential participation in reward circuitry
Open accessAbstract
The dorsal raphe nucleus (DRN) contains the largest group of serotonin-producing neurons in the brain and projects to regions controlling reward. Although pharmacological studies suggest that serotonin inhibits reward seeking, electrical stimulation of the DRN strongly reinforces instrumental behavior. Here, we provide a targeted assessment of the behavioral, anatomical, and electrophysiological contributions of serotonergic and nonserotonergic DRN neurons to reward processes. To explore DRN heterogeneity, we used a simultaneous two-vector knockout/optogenetic stimulation strategy, as well as cre-induced and cre-silenced vectors in several cre-expressing transgenic mouse lines. We found that the DRN is capable of reinforcing behavior primarily via nonserotonergic neurons, for which the main projection target is the ventral tegmental area (VTA). Furthermore, these nonserotonergic projections provide glutamatergic excitation of VTA dopamine neurons and account for a large majority of the DRN-VTA pathway. These findings help to resolve apparent discrepancies between the roles of serotonin versus the DRN in behavioral reinforcement.
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DR and MR contain GABAergic and glutamatergic neurons that do not express Tph2, some of which may project to the same target regions.
“However, DR and MR contain not only serotonin neurons but also GABAergic and glutamatergic neurons that do not express Tph2 (and hence do not release serotonin), some of which may project to the same target regions (McDevitt et al., 2014).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as McDevitt et al., 2014
DRN and VTA DA neurons may be functionally distinct.
“Amid the sparse existing knowledge of the functional role of DRN DA neurons, optical stimulation of these neurons does not support intra-cranial self-stimulation (ICSS) (McDevitt et al., 2014), in contrast to the VTA (Witten et al., 2011), suggesting that DRN and VTA DA neurons may be functionally distinct.”
From Dorsal raphe dopamine neurons represent the experience of social isolation (2016) · cites this paper as McDevitt et al., 2014
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References 63 · Cited by 203
- Authors
- McDevitt, R. A., Tiran-Cappello, A., Shen, H., Balderas, I., Britt, J. P., Marino, R. A. M., Chung, S. L., Richie, C. T., Harvey, B. K., & Bonci, A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Bonci, Antonello
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 8
- Issue
- 6
- Pages
- 1857-1869
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4181379
- OpenAlex
- W2052257860
- Cited by
- 203
- References
- 63
- Citations by year
- 2026: 15 · 2025: 7 · 2024: 13 · 2023: 18 · 2022: 12 · 2021: 18 · 2020: 16 · 2019: 18 · 2018: 17 · 2017: 25 · 2016: 20 · 2015: 24
- FWCI
- 10.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (Z99 DA999999)
- National Institute on Drug Abuse
- 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
- dorsal raphe nucleus, serotonergic neurons, reward systems, behavioral reinforcement, ventral tegmental area, dopaminergic neurons, glutamatergic excitation, optogenetic stimulation, knockout mice, neuronal heterogeneity
- MeSH terms
- Amphetamine, Animals, Dopamine, Female, Fenfluramine, Male, Mice, Inbred C57BL, Mice, Transgenic, Serotonin, Ventral Tegmental Area, Mice, Dopaminergic Neurons, Serotonergic Neurons, GABAergic Neurons, Dorsal Raphe Nucleus
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