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Corticotropin-Releasing Factor Increases In Vitro Firing Rates of Serotonergic Neurons in the Rat Dorsal Raphe Nucleus: Evidence for Activation of a Topographically Organized Mesolimbocortical Serotonergic System
Open accessAbstract
In vivo studies suggest that the stress-related neuropeptide corticotropin-releasing factor (CRF) modulates serotonergic neurotransmission. To investigate the underlying mechanisms for this interaction, the present study examined the effects of CRF in vitro on dorsal raphe neurons that displayed electrophysiological and pharmacological properties consistent with a serotonergic phenotype. In the presence of either 1 or 2 mm Ca(2+), perfusion of ovine CRF or rat/human CRF rapidly and reversibly increased firing rates of a subpopulation (19 of 70, 27%) of serotonergic neurons predominantly located in the ventral portion of the dorsal raphe nucleus. For a given responsive neuron, the excitatory effects of CRF were reproducible, and there was no tachyphylaxis. Excitatory effects were dose-dependent (over the range of 0.1-1.6 micrometer) and were completely absent after exposure to the competitive CRF receptor antagonists alpha-helical CRF(9-41) or rat/human [d-Phe(12), Nle(21, 38), alpha-Me-Leu(37)]-CRF(12-41). Both the proportion of responsive neurons and the magnitude of excitatory responses to CRF in the ventral portion of the caudal dorsal raphe nucleus were markedly potentiated in slices prepared from animals previously exposed to isolation and daily restraint stress for 5 d. Immunohistochemical staining of the recorded slices revealed close associations between CRF-immunoreactive varicose axons and tryptophan hydroxylase-immunoreactive neurons in the area of the recordings, providing anatomical evidence for potential direct actions of CRF on serotonergic neurons. The electrophysiological properties and the distribution of responsive neurons within the dorsal raphe nucleus are consistent with the hypothesis that endogenous CRF activates a topographically organized mesolimbocortical serotonergic system.
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“Although DRN 5-HT neurons share a common developmental lineage (Deneris and Gaspar, 2018; Jensen et al., 2008), DRN 5-HT neurons in different subregions express different G protein-coupled receptors and vesicular transporters, suggesting spatial clustering of functionally specialized neurons (Calizo et al., 2011; Fernandez et al., 2016; Lowry et al., 2000; Templin et al., 2012).”
From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Lowry et al., 2000
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“Even bona fide DRN 5-HT neurons are molecularly, anatomically, and physiologically heterogeneous.”
From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Lowry et al., 2000
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- Lowry, 1999, Corticotropin-releasing factor (CRF) increases in vitro firing rates of serotonergic neurones in the rat dorsal raphe nucleus: evidence for selective activation of a topographically organised mesolimbocortical serotonergic system., Soc Neurosci Abstr, 25, 75
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Metadata
- Authors
- Lowry, C. A., Rodda, J. E., Lightman, S. L., & Ingram, C. D.
- Affiliations
- University of Bristol (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-10-15
- Volume
- 20
- Issue
- 20
- Pages
- 7728-7736
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772886
- OpenAlex
- W2109594449
- Cited by
- 211
- References
- 113
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 5 · 2012: 8
- FWCI
- 5.00
- 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)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (045843/Z/95/Z)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- corticotropin-releasing factor, dorsal raphe nucleus, serotonergic neurons, neuronal firing rate, CRF receptor antagonists, tryptophan hydroxylase, stress, isolation stress, restraint stress, topographic organization
- MeSH terms
- Action Potentials, Animals, Axons, Calcium, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Immunohistochemistry, Male, Microelectrodes, Synaptic Transmission, Neurons, Raphe Nuclei, Reaction Time, Restraint, Physical, Serotonin, Stress, Physiological, Tryptophan Hydroxylase, Rats, Wistar, Serotonin Receptor Agonists, Rats, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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