Activity of Raphé serotonergic neurons controls emotional behaviors
Open accessAbstract
Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function.
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Recent studies on acute activation of DR serotonin neurons have reported divergent findings, including reinforcement, promotion of waiting for delayed reward, promotion of anxiety-like behaviors and suppression of locomotion, and suppression of locomotion without effects on reinforcement or anxiety-like behaviors.
“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 Teissier et al., 2015
The DR serotonin system negatively regulates locomotion.
“The DR serotonin system has been consistently shown to negatively regulate locomotion (Correia et al., 2017; Teissier et al., 2015; Whitney et al., 2016).”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Teissier et al., 2015
Chemogenetic activation of DR serotonin neurons reduces immobility in the forced-swim test.
“Chemogenetic activation of DR serotonin neurons has recently been reported to reduce immobility in the forced-swim test (Teissier et al., 2015).”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Teissier et al., 2015
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“A likely candidate for this effect is the ratio of median to dorsal raphe activity, which has been shown to correlate with anxiety in the postnatal FLX model of anxietydepression (Teissier et al., 2015).”
Background
- Authors
- Teissier, A., Chemiakine, A., Inbar, B., Bagchi, S., Ray, R. S., Palmiter, R. D., Dymecki, S. M., Moore, H., & Ansorge, M. S.
- Affiliations
- Columbia University (US)
- New York State Psychiatric Institute (US)
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ansorge, Mark S.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 13
- Issue
- 9
- Pages
- 1965-1976
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4756479
- OpenAlex
- W2173725389
- Cited by
- 197
- References
- 50
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 20 · 2023: 12 · 2022: 13 · 2021: 27 · 2020: 23 · 2019: 28 · 2018: 16 · 2017: 17 · 2016: 11
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Mental Health (R00MH083044, R01MH099118)
- National Institute on Drug Abuse (R21DA023643)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- serotonergic neurons, dorsal raphe nucleus, median raphe, serotonin signaling, anxiety, depression-like behavior, emotion regulation, forced swim test, neuronal hyperactivity
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Cell Line, Clozapine, Depressive Disorder, Disease Models, Animal, Female, Male, Mice, Transgenic, Serotonin, Swimming, Mice, Serotonergic Neurons
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