Htr2a gene and 5-HT2A receptor expression in the cerebral cortex studied using genetically modified mice
Frontiers in Neuroscience 2010 DOI: 10.3389/fnins.2010.00036 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study using transgenic and knockout mice Peer reviewed |
|---|---|
| Population | Genetically modified mice |
| Topics | Serotonin |
| Keywords | Parvalbumin Gabaergic Cortex anatomy Receptor Pyramidal cell Neocortex Cerebral cortex Cell biology Hippocampus Inhibitory postsynaptic potential Genetics |
| Citations | 201 |
| Key findings | 5-HT(2A) receptors are expressed in three main cortical neuronal populations: layer V pyramidal cells, GABAergic interneurons of middle layers, and subplate/Layer VIb non-pyramidal cells, with most GABAergic interneurons being parvalbumin-expressing fast-spiking cells depolarized by serotonin. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 82
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Broadband Cortical Desynchronization Underlies the Human Psychedelic State Journal of Neuroscience September 18, 2013
- Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology November 1, 2020
- Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. Neuroimage May 25, 2019
- Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution Frontiers in Human Neuroscience May 23, 2017
and 77 more in the library
Cites 4
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism Journal of Neuroscience December 15, 2001
- PSD-95 Is Essential for Hallucinogen and Atypical Antipsychotic Drug Actions at Serotonin Receptors Journal of Neuroscience June 3, 2009
- Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proceedings of the National Academy of Sciences June 5, 2007