NMDA receptors trigger neurosecretion of 5-HT within dorsal raphe nucleus of the rat in the absence of action potential firing
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Activity and calcium-dependent release of neurotransmitters from the somatodendritic compartment is an important signalling mechanism between neurones throughout the brain. NMDA receptors and vesicles filled with neurotransmitters occur in close proximity in many brain areas. It is unknown whether calcium influx through these receptors can trigger the release of somatodendritic vesicles directly, or whether postsynaptic action potential firing is necessary for release of these vesicles. Here we addressed this question by studying local release of serotonin (5-HT) from dorsal raphé nucleus (DRN) neurones. We performed capacitance measurements to monitor the secretion of vesicles in giant soma patches, in response to short depolarizations and action potential waveforms. Amperometric measurements confirmed that secreted vesicles contained 5-HT. Surprisingly, two-photon imaging of DRN neurones in slices revealed that dendritic calcium concentration changes in response to somatic firing were restricted to proximal dendritic areas. This implied that alternative calcium entry pathways may dominate the induction of vesicle secretion from distal dendrites. In line with this, transient NMDA receptor activation, in the absence of action potential firing, was sufficient to induce capacitance changes. By monitoring GABAergic transmission onto DRN 5-HT neurones in slices, we show that endogenous NMDA receptor activation, in the absence of postsynaptic firing, induced release of 5-HT, which in turn increased the frequency of GABAergic inputs through activation of 5-HT(2) receptors. We propose here that calcium influx through NMDA receptors can directly induce postsynaptic 5-HT release from DRN neurones, which in turn may facilitate GABAergic input onto these cells.
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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 de Kock et al., 2006
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Molecular and anatomical organization of the dorsal raphe nucleus
Huang, K. W., Ochandarena, N. E., Philson, A. C., Hyun, M., Birnbaum, J. E., Cicconet, M., & Sabatini, B. L. (2019) · eLife · doi:10.7554/elife.46464 · Cited by 267 · see citing works
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Gölöncsér, F., Baranyi, M., Balázsfi, D., Demeter, K., Haller, J., Freund, T. F. F., Zelena, D., & Sperlágh, B. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00325 · Cited by 25 · see citing works
- Authors
- De Kock, C. P. J., Cornelisse, L. N., Burnashev, N., Lodder, J. C., Timmerman, A. J., Couey, J. J., Mansvelder, H. D., & Brussaard, A. B.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Brussaard, A. B.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2006-12-07
- Volume
- 577
- Issue
- 3
- Pages
- 891-905
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC1890386
- OpenAlex
- W2104890744
- Cited by
- 55
- References
- 66
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- NMDA receptor, serotonin release, dorsal raphe nucleus, dendritic calcium influx, GABAergic inhibition, 5-HT2 receptor, calcium-dependent neurotransmitter release, dendritic calcium signaling
- MeSH terms
- Action Potentials, Animals, Calcium, Dendrites, Neurons, Osmolar Concentration, Raphe Nuclei, Serotonin, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Electric Capacitance, Receptors, Serotonin, 5-HT2, Rats, In Vitro Techniques
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