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Dorsal Raphe Neurons Signal Reward through 5-HT and Glutamate
Open accessAbstract
The dorsal raphe nucleus (DRN) in the midbrain is a key center for serotonin (5-hydroxytryptamine; 5-HT)-expressing neurons. Serotonergic neurons in the DRN have been theorized to encode punishment by opposing the reward signaling of dopamine neurons. Here, we show that DRN neurons encode reward, but not punishment, through 5-HT and glutamate. Optogenetic stimulation of DRN Pet-1 neurons reinforces mice to explore the stimulation-coupled spatial region, shifts sucrose preference, drives optical self-stimulation, and directs sensory discrimination learning. DRN Pet-1 neurons increase their firing activity during reward tasks, and this activation can be used to rapidly change neuronal activity patterns in the cortex. Although DRN Pet-1 neurons are often associated with 5-HT, they also release glutamate, and both neurotransmitters contribute to reward signaling. These experiments demonstrate the ability of DRN neurons to organize reward behaviors and might provide insights into the underlying mechanisms of learning facilitation and anhedonia treatment.
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In the citing paper
“Optogenetic stimulation of DRN neurons led to exploration of stimulation-coupled spatial regions, shift in sucrose preference, optical self-stimulation, and guidance of sensory discrimination learning on a behavioral level.”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Liu et al., 2014
In the citing paper
“Blockage of either serotonin synthesis or glutamate release resulted in partial impairments in reward experiments (Liu et al., 2014).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Liu et al., 2014
In the citing paper
“Importantly, an animal study showed that the DRN increases firing rates during reward-associated tasks and that effects are mediated via the serotonergic and glutamatergic system on a postsynaptic level.”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Liu et al., 2014
In the citing paper
“~60% of DR serotonin neurons co-express the vesicular glutamate transporter Vglut3 in the rat (Gras et al., 2002) and co-release glutamate in the mouse (Liu et al., 2014; Sengupta et al., 2017).”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Liu et al., 2014
In the citing paper
“recent studies on the effects of acute activation of DR serotonin neurons have reported divergent findings, including reinforcement (Liu et al., 2014), promotion of waiting for delayed reward rather than reinforcement (Fonseca et al., 2015; Miyazaki et al., 2012), promotion of anxiety-like behaviors and suppression of locomotion (Teissier et al., 2015; Urban et al., 2016), and suppression of locom”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Liu et al., 2014
In the citing paper
“Glutamate co-release from Vglut3+ serotonin terminals has indeed been reported at the hippocampus (Varga et al., 2009), orbital prefrontal cortex (Ren et al., 2018), nucleus accumbens (Liu et al., 2014), ventral tegmental area (Wang et al., 2019), and basolateral amygdala (Sengupta et al., 2017).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Liu et al., 2014
In the citing paper
“For example, several studies have reported that subgroups of serotonin neurons in the MR and DR express Vglut3 and indeed, subsequent slice recording confirmed that serotonin terminals can co-release glutamate and serotonin (Domonkos et al., 2016; Liu et al., 2014; Ren et al., 2018; Sengupta et al., 2017; Varga et al., 2009; Wang et al., 2019).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Liu et al., 2014
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Metadata
- Authors
- Liu, Z., Zhou, J., Li, Y., Hu, F., Lu, Y., Ma, M., Feng, Q., Zhang, J.-E., Wang, D., Zeng, J., Bao, J., Kim, J.-Y., Chen, Z.-F., El Mestikawy, S., & Luo, M.
- Affiliations
- Beijing Normal University (CN)
- Peking University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Washington University in St. Louis (US)
- Corresponding author
- Luo, Minmin
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 81
- Issue
- 6
- Pages
- 1360-1374
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4411946
- OpenAlex
- W2060357443
- Cited by
- 469
- References
- 68
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 41 · 2023: 39 · 2022: 28 · 2021: 39 · 2020: 39 · 2019: 44 · 2018: 41 · 2017: 46 · 2016: 45 · 2015: 35 · 2014: 18
- FWCI
- 21.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR056318, AR056318)
- 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, serotonin, glutamate, reward signaling, optogenetic stimulation, sucrose preference, self-stimulation, anhedonia, dopamine, punishment
- MeSH terms
- Animals, Behavior, Animal, Mesencephalon, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Raphe Nuclei, Reward, Serotonin, Glutamic Acid, Mice
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