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Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice

Ketamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for th...

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Autores principales: Rawat, Radhika, Tunc-Ozcan, Elif, McGuire, Tammy L., Peng, Chian-Yu, Kessler, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098911/
https://www.ncbi.nlm.nih.gov/pubmed/35551462
http://dx.doi.org/10.1038/s41467-022-30386-5
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author Rawat, Radhika
Tunc-Ozcan, Elif
McGuire, Tammy L.
Peng, Chian-Yu
Kessler, John A.
author_facet Rawat, Radhika
Tunc-Ozcan, Elif
McGuire, Tammy L.
Peng, Chian-Yu
Kessler, John A.
author_sort Rawat, Radhika
collection PubMed
description Ketamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine treatment activates ABINs in parallel with its behavioral effects in both stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks the antidepressant effects of ketamine, indicating that this activity is necessary for the behavioral effects. Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects. These findings thus identify a specific cell population that mediates the antidepressant actions of ketamine, indicating that ABINs can potentially be targeted to limit ketamine’s side effects while preserving its therapeutic efficacy.
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spelling pubmed-90989112022-05-14 Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice Rawat, Radhika Tunc-Ozcan, Elif McGuire, Tammy L. Peng, Chian-Yu Kessler, John A. Nat Commun Article Ketamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine treatment activates ABINs in parallel with its behavioral effects in both stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks the antidepressant effects of ketamine, indicating that this activity is necessary for the behavioral effects. Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects. These findings thus identify a specific cell population that mediates the antidepressant actions of ketamine, indicating that ABINs can potentially be targeted to limit ketamine’s side effects while preserving its therapeutic efficacy. Nature Publishing Group UK 2022-05-12 /pmc/articles/PMC9098911/ /pubmed/35551462 http://dx.doi.org/10.1038/s41467-022-30386-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rawat, Radhika
Tunc-Ozcan, Elif
McGuire, Tammy L.
Peng, Chian-Yu
Kessler, John A.
Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
title Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
title_full Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
title_fullStr Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
title_full_unstemmed Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
title_short Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
title_sort ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098911/
https://www.ncbi.nlm.nih.gov/pubmed/35551462
http://dx.doi.org/10.1038/s41467-022-30386-5
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