Dorsal raphe dual serotonin-glutamate neurons drive reward by establishing excitatory synapses on VTA mesoaccumbens dopamine neurons

Wang, Hui-Ling; Zhang, Shiliang; Qi, Jia; Wang, Huikun; Cachope, Roger; Mejias-Aponte, Carlos A.; Gomez, Jorge A.; Mateo-Semidey, Gabriel E.; Beaudoin, Gerard M.J.; Paladini, Carlos A.; Cheer, Joseph F.; Morales, Marisela

doi:10.1016/j.celrep.2019.01.014

Cited by 176Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeural and Behavioral Psychology Studies

Dorsal raphe dual serotonin-glutamate neurons drive reward by establishing excitatory synapses on VTA mesoaccumbens dopamine neurons

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Wang, Hui-Ling, Zhang, Shiliang, Qi, Jia, Wang, Huikun, Cachope, Roger, Mejias-Aponte, Carlos A., Gomez, Jorge A., Mateo-Semidey, Gabriel E. +4 more·2019·Cell Reports

DOI 10.1016/j.celrep.2019.01.014PMC PMC6489450

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Abstract

Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons.

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5-HT/vGluT3+ neurons from the dorsal raphe target the VTA, make asymmetric synapses, and monosynaptically release glutamate to excite accumbal-projecting dopamine neurons.
“5-HT/vGluT3+ neurons from the dorsal raphe also target the VTA, where they make asymmetric synapses and monosynaptically release glutamate to excite accumbal-projecting dopamine neurons.79”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [79]

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Authors: Wang, H.-L., Zhang, S., Qi, J., Wang, H., Cachope, R., Mejias-Aponte, C. A., Gomez, J. A., Mateo-Semidey, G. E., Beaudoin, G. M. J., Paladini, C. A., Cheer, J. F., & Morales, M.
Affiliations: National Institutes of Health (US)
University of Maryland, Baltimore (US)
The University of Texas at San Antonio (US)
Corresponding author: Morales, Marisela
ORCID: Zhang, Shiliang
Qi, Jia
Wang, Huikun
Cachope, Roger
Beaudoin, Gerard M.J.
Paladini, Carlos A.
Cheer, Joseph F.
Morales, Marisela
Venue: Cell Reports
Publisher: Elsevier BV
Published: 2019-01
Volume: 26
Issue: 5
Pages: 1128-1142.e7
ISSN: 2211-1247 (ISSN-L)
DOI: 10.1016/j.celrep.2019.01.014
PMC: PMC6489450
OpenAlex: W2912884060
Cited by: 176
References: 91
Citations by year: 2026: 17 · 2025: 21 · 2024: 19 · 2023: 22 · 2022: 13 · 2021: 31 · 2020: 39 · 2019: 14
FWCI: 11.58
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 3 d)
Locations: Cell Reports (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
PubMed Central (acceptedVersion, cc-by-nc-nd)
Digital Commons - Trinity University (Trinity University) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute of Mental Health (R01MH107229, R21MH113341)
National Institute on Drug Abuse (R01DA038453, R01DA042595, F31DA041303, R01DA022340)
National Institute of General Medical Sciences (R25GM060655)
National Institute of Neurological Disorders and Stroke (P30NS050274)
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, serotonin transporter, VGLUT3, ventral tegmental area, asymmetric synapses, glutamate release, reward, conditioned place preference, nucleus accumbens dopamine release
MeSH terms: Animals, Axons, Male, Mice, Inbred C57BL, Nucleus Accumbens, Reward, Serotonin, Synapses, Ventral Tegmental Area, Glutamic Acid, Amino Acid Transport Systems, Acidic, Dopaminergic Neurons, Dorsal Raphe Nucleus

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Dorsal raphe dual serotonin-glutamate neurons drive reward by establishing excitatory synapses on VTA mesoaccumbens dopamine neurons

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