Embracing diversity in the 5-HT neuronal system
Abstract
Neurons that synthesize and release 5-hydroxytryptamine (5-HT; serotonin) express a core set of genes that establish and maintain this neurotransmitter phenotype and distinguish these neurons from other brain cells. Beyond a shared 5-HTergic phenotype, these neurons display divergent cellular properties in relation to anatomy, morphology, hodology, electrophysiology and gene expression, including differential expression of molecules supporting co-transmission of additional neurotransmitters. This diversity suggests that functionally heterogeneous subtypes of 5-HT neurons exist, but linking subsets of these neurons to particular functions has been technically challenging. We discuss recent data from molecular genetic, genomic and functional methods that, when coupled with classical findings, yield a reframing of the 5-HT neuronal system as a conglomeration of diverse subsystems with potential to inspire novel, more targeted therapies for clinically distinct 5-HT-related disorders.
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The DR and MR serotonin systems differ in developmental origin, connectivity, physiology, and behavioral function.
“Evidence has suggested that the DR and MR serotonin systems differ in developmental origin, connectivity, physiology, and behavioral function (Alonso et al., 2013; Calizo et al., 2011; Okaty 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 Okaty et al., 2019
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Selective filtering of excitatory inputs to nucleus accumbens by dopamine and serotonin
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Serotonergic neuromodulation of synaptic plasticity
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Serotonergic reinforcement of a complete swallowing circuit
Schoofs, A., Miroschnikow, A., Schlegel, P., Zinke, I., Schneider-Mizell, C. M., Cardona, A., & Pankratz, M. J. (2023) · doi:10.1101/2023.05.26.542464 · Cited by 7 · see citing works
- Authors
- Okaty, B. W., Commons, K. G., & Dymecki, S. M.
- Affiliations
- Harvard University (US)
- Boston Children's Hospital (US)
- Corresponding author
- Okaty, Benjamin W.
- Dymecki, Susan M.
- Venue
- Nature Reviews Neuroscience
- Published
- 2019-04-04
- Volume
- 20
- Issue
- 7
- Pages
- 397-424
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2930394955
- Semantic Scholar
- 314ef2487880bf48b66f770330b066e3d4e9d6fd
- Cited by
- 319
- References
- 331
- Citations by year
- 2026: 47 · 2025: 57 · 2024: 47 · 2023: 54 · 2022: 49 · 2021: 32 · 2020: 25 · 2019: 8
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (R21DA023643, R01DA021801)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD036379)
- 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 › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- serotonin, serotonergic neurons, neuronal heterogeneity, co-transmission, neuronal morphology, neuronal electrophysiology, neuronal cell types, targeted therapy
- MeSH terms
- Animals, Brain, Humans, Serotonin, Serotonergic Neurons, Transcriptome
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