Htr2a gene and 5-HT2A receptor expression in the cerebral cortex studied using genetically modified mice
Open accessAbstract
Serotonin receptors of the 5-HT(2A) subtype are robustly expressed in the cerebral cortex where they have been implicated in the pathophysiology and therapeutics of mental disorders and the actions of hallucinogens. Much less is known, however, about the specific cell types expressing 5-HT(2A) receptors in cortex. In the current study we use immunohistochemical and electrophysiological approaches in genetically modified mice to address the expression of the Htr2a gene and 5-HT(2A) receptors in cortex. We first use an EGFP-expressing BAC transgenic mice and identify three main Htr2A gene expressing neuronal populations in cortex. The largest of these cell populations corresponds to layer V pyramidal cells of the anterior cortex, followed by GABAergic interneurons of the middle layers, and non-pyramidal cells of the subplate/Layer VIb. We then use 5-HT(2A) receptor knockout mice to identify an antibody capable of localizing 5-HT(2A) receptors in brain and use it to map these receptors. We find strong laminar expression of 5-HT(2A) receptors in cortex, especially along a diffuse band overlaying layer Va. This band exhibits a strong anteroposterior gradient that closely matches the localization of Htr2A expressing pyramidal cells of layer V. Finally we use electrophysiological and immunohistochemical approaches to show that most, but not all, GABAergic interneurons of the middle layers are parvalbumin expressing Fast-spiking interneurons and that these cells are depolarized and excited by serotonin, most likely through the activation of 5-HT(2A) receptors. These results clarify and extend our understanding of the cellular distribution of 5-HT(2A) receptors in the cerebral cortex.
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In rodents, the 5-HT2A receptor expression pattern has been confirmed using immunohistochemistry, light and electron microscope immunocytochemistry, in situ hybridization, receptor autoradiography, and transgenic mice expressing EGFP under control of the 5-HT2A receptor promoter.
“In rodents, this expression pattern has been confirmed using immunohistochemistry (203–206), light and electron microscope immunocytochemistry (203), in situ hybridization (207, 208), receptor autoradiography (209), and transgenic mice expressing EGFP under control of the 5-HT2A receptor promoter (210).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [210]
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- Authors
- Weber
- Affiliations
- Wayne State University (US)
- Corresponding author
- Weber
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2010
- Volume
- 4
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC2928707
- OpenAlex
- W2166045982
- Cited by
- 205
- References
- 53
- Citations by year
- 2026: 16 · 2025: 10 · 2024: 16 · 2023: 17 · 2022: 17 · 2021: 17 · 2020: 13 · 2019: 14 · 2018: 12 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH043985)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- HTR2A, 5-HT2A receptor, cerebral cortex, serotonin receptors, cortical cell types, layer 5 pyramidal neurons, GABAergic interneurons, parvalbumin interneurons, fast-spiking interneurons, receptor knockout mice, BAC transgenic mice
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