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Modulation of anxiety by cortical serotonin 1A receptors

Serotonin (5-HT) plays an important role in the modulation of behavior across animal species. The serotonin 1A receptor (Htr1a) is an inhibitory G-protein coupled receptor that is expressed both on serotonin and non-serotonin neurons in mammals. Mice lacking Htr1a show increased anxiety behavior sug...

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Autores principales: Piszczek, Lukasz, Piszczek, Agnieszka, Kuczmanska, Joanna, Audero, Enrica, Gross, Cornelius T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338812/
https://www.ncbi.nlm.nih.gov/pubmed/25759645
http://dx.doi.org/10.3389/fnbeh.2015.00048
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author Piszczek, Lukasz
Piszczek, Agnieszka
Kuczmanska, Joanna
Audero, Enrica
Gross, Cornelius T.
author_facet Piszczek, Lukasz
Piszczek, Agnieszka
Kuczmanska, Joanna
Audero, Enrica
Gross, Cornelius T.
author_sort Piszczek, Lukasz
collection PubMed
description Serotonin (5-HT) plays an important role in the modulation of behavior across animal species. The serotonin 1A receptor (Htr1a) is an inhibitory G-protein coupled receptor that is expressed both on serotonin and non-serotonin neurons in mammals. Mice lacking Htr1a show increased anxiety behavior suggesting that its activation by serotonin has an anxiolytic effect. This outcome can be mediated by either Htr1a population present on serotonin (auto-receptor) or non-serotonin neurons (hetero-receptor), or both. In addition, both transgenic and pharmacological studies have shown that serotonin acts on Htr1a during development to modulate anxiety in adulthood, demonstrating a function for this receptor in the maturation of anxiety circuits in the brain. However, previous studies have been equivocal about which Htr1a population modulates anxiety behavior, with some studies showing a role of Htr1a hetero-receptor and others implicating the auto-receptor. In particular, cell-type specific rescue and suppression of Htr1a expression in either forebrain principal neurons or brainstem serotonin neurons reached opposite conclusions about the role of the two populations in the anxiety phenotype of the knockout. One interpretation of these apparently contradictory findings is that the modulating role of these two populations depends on each other. Here we use a novel Cre-dependent inducible allele of Htr1a in mice to show that expression of Htr1a in cortical principal neurons is sufficient to modulate anxiety. Together with previous findings, these results support a hetero/auto-receptor interaction model for Htr1a function in anxiety.
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spelling pubmed-43388122015-03-10 Modulation of anxiety by cortical serotonin 1A receptors Piszczek, Lukasz Piszczek, Agnieszka Kuczmanska, Joanna Audero, Enrica Gross, Cornelius T. Front Behav Neurosci Neuroscience Serotonin (5-HT) plays an important role in the modulation of behavior across animal species. The serotonin 1A receptor (Htr1a) is an inhibitory G-protein coupled receptor that is expressed both on serotonin and non-serotonin neurons in mammals. Mice lacking Htr1a show increased anxiety behavior suggesting that its activation by serotonin has an anxiolytic effect. This outcome can be mediated by either Htr1a population present on serotonin (auto-receptor) or non-serotonin neurons (hetero-receptor), or both. In addition, both transgenic and pharmacological studies have shown that serotonin acts on Htr1a during development to modulate anxiety in adulthood, demonstrating a function for this receptor in the maturation of anxiety circuits in the brain. However, previous studies have been equivocal about which Htr1a population modulates anxiety behavior, with some studies showing a role of Htr1a hetero-receptor and others implicating the auto-receptor. In particular, cell-type specific rescue and suppression of Htr1a expression in either forebrain principal neurons or brainstem serotonin neurons reached opposite conclusions about the role of the two populations in the anxiety phenotype of the knockout. One interpretation of these apparently contradictory findings is that the modulating role of these two populations depends on each other. Here we use a novel Cre-dependent inducible allele of Htr1a in mice to show that expression of Htr1a in cortical principal neurons is sufficient to modulate anxiety. Together with previous findings, these results support a hetero/auto-receptor interaction model for Htr1a function in anxiety. Frontiers Media S.A. 2015-02-24 /pmc/articles/PMC4338812/ /pubmed/25759645 http://dx.doi.org/10.3389/fnbeh.2015.00048 Text en Copyright © 2015 Piszczek, Piszczek, Kuczmanska, Audero and Gross. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Piszczek, Lukasz
Piszczek, Agnieszka
Kuczmanska, Joanna
Audero, Enrica
Gross, Cornelius T.
Modulation of anxiety by cortical serotonin 1A receptors
title Modulation of anxiety by cortical serotonin 1A receptors
title_full Modulation of anxiety by cortical serotonin 1A receptors
title_fullStr Modulation of anxiety by cortical serotonin 1A receptors
title_full_unstemmed Modulation of anxiety by cortical serotonin 1A receptors
title_short Modulation of anxiety by cortical serotonin 1A receptors
title_sort modulation of anxiety by cortical serotonin 1a receptors
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338812/
https://www.ncbi.nlm.nih.gov/pubmed/25759645
http://dx.doi.org/10.3389/fnbeh.2015.00048
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