Control of Dorsal Raphe Serotonergic Neurons by the Medial Prefrontal Cortex: Involvement of Serotonin-1A, GABAA, and Glutamate Receptors
Open accessAbstract
Anatomical evidence indicates that medial prefrontal cortex (mPFC) neurons project to the dorsal raphe nucleus (DR). In this study, we functionally characterized this descending pathway in rat brain. Projection neurons in the mPFC were identified by antidromic stimulation from the DR. Electrical stimulation of the mPFC mainly inhibited the activity of DR 5-HT neurons (55 of 66). Peristimulus time histograms showed a silence of 150 ± 9 msec poststimulus (latency, 36 ± 1 msec). The administration of WAY-100635 and picrotoxinin partly reversed this inhibition, indicating the involvement of 5-HT 1A and GABA A receptors. In rats depleted of 5-HT with p-chlorophenylalanine, the electrical stimulation of mPFC mainly activated 5-HT neurons (31 of 40). The excitations (latency, 17 ± 1 msec) were antagonized by MK-801 and NBQX. Likewise, MK-801 prevented the rise in DR 5-HT release induced by electrical stimulation of mPFC. The application of 8-OH-DPAT in mPFC significantly inhibited the firing rate of DR 5-HT neurons and, in dual-probe microdialysis experiments, reduced the 5-HT output in mPFC and DR. Furthermore, the application of WAY-100635 in mPFC significantly antagonized the reduction of 5-HT release produced by systemic 8-OH-DPAT administration in both areas. These results indicate the existence of a complex regulation of DR 5-HT neurons by mPFC afferents. The stimulus-induced excitation of some 5-HT neurons by descending excitatory fibers releases 5-HT, which inhibits the same or other DR neurons by acting on 5-HT 1A autoreceptors. Afferents from the mPFC also inhibit 5-HT neurons through the activation of GABAergic interneurons. Ascending serotonergic pathways may control the activity of this descending pathway by acting on postsynaptic 5-HT 1A receptors.
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DRN serotonergic neurons are controlled by glutamatergic projections from the PFC.
“In addition, DRN serotonergic neurons are controlled by glutamatergic projections from the PFC [152, 207–209].”
From Development of prefrontal cortex (2022) · cites this paper as [152]
Glutamatergic signaling can control the release of serotonin from the dorsal raphe nucleus.
“glutamatergic signaling can also control the release of serotonin from the dorsal raphe nucleus (Celada et al., 2001).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Celada et al., 2001
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References 67 · Cited by 497
Research works printed but not linked: 2
- Hjorth S, Carlsson A, Magnusson T, Arvidsson LE (1987) In vivo char- acterization of 8-OH-DPAT: evidence for 5-HT receptor selectivity and agonist action in the rat CNS. In: Brain 5-HT1A receptors, (Dour- ish CT, Ahlenius S, Hutson PH, eds), pp. 94 -105. Chichester, UK: Ellis Horwood.
- Myers RD (1971) Methods for chemical stimulation of the brain. In: Methods of psychobiology, Vol 1 (Myers RD, ed), pp 247-280. New York: Academic.
- Authors
- Celada, P., Puig, M. V., Casanovas, J. M., Guillazo, G., & Artigas, F.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-12-15
- Volume
- 21
- Issue
- 24
- Pages
- 9917-9929
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763042
- OpenAlex
- W1543276710
- Cited by
- 497
- References
- 67
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 18 · 2021: 15 · 2020: 18 · 2019: 15 · 2018: 19 · 2017: 20 · 2016: 19 · 2015: 28 · 2014: 32 · 2013: 29 · 2012: 26
- FWCI
- 6.28
- 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)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- 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
- medial prefrontal cortex, dorsal raphe nucleus, serotonergic neurons, 5-HT1A receptor, GABAA receptor, glutamate receptors, descending serotonergic pathways, serotonin autoreceptors, 8-OH-DPAT, WAY-100635, picrotoxinin, MK-801, NBQX, p-chlorophenylalanine, serotonin release, GABAergic interneurons
- MeSH terms
- Animals, Catheterization, Electric Stimulation, Evoked Potentials, Male, Neural Inhibition, Neural Pathways, Neurons, Raphe Nuclei, Reaction Time, Receptors, GABA-A, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Prefrontal Cortex, Receptors, Glutamate, Microdialysis, Autoreceptors, Receptors, Neurotransmitter, Excitatory Amino Acid Antagonists, GABA Antagonists, Receptors, Serotonin, 5-HT1, Rats, GABA-A Receptor Antagonists
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