Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites
Open accessAbstract
Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here, three-photon microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence, and immunogold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca(2+) channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines, and NMDA receptor antagonists.
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5-HT can be released somatodendritically and from 5-HT axon terminals in the DRN.
“As 5-HT can be released somatodendritically and from 5-HT axon terminals in the DRN (Colgan et al., 2012; de Kock et al., 2006; Kaushalya et al., 2008), we examined the expression patterns of 5-HT receptors in the dataset to infer local 5-HT signaling.”
From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Colgan et al., 2012
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- Authors
- Colgan, L. A., Cavolo, S. L., Commons, K. G., & Levitan, E. S.
- Affiliations
- University of Pittsburgh (US)
- Harvard University (US)
- Corresponding author
- Levitan, Edwin S.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-11-07
- Volume
- 32
- Issue
- 45
- Pages
- 15737-15746
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3505755
- OpenAlex
- W1988606802
- Cited by
- 48
- References
- 42
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 5 · 2012: 1
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (R21DA025739, R21 DA25739, R01DA021801, DA21801)
- National Institute of Neurological Disorders and Stroke (R01-NS32385, R01NS032385)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- dorsal raphe nucleus, serotonergic neurons, vesicular monoamine transporter 2, glutamate receptors, NMDA receptor, L-type calcium channels, fluoxetine, selective serotonin reuptake inhibitors, antidepressant mechanism, three-photon microscopy
- MeSH terms
- Action Potentials, Animals, Dendrites, Fluoxetine, Male, Neurons, Serotonin, N-Methylaspartate, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Excitatory Amino Acid Agonists, Calcium Channels, L-Type, Secretory Vesicles, Vesicular Monoamine Transport Proteins, Rats
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