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A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances

In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupt...

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Autores principales: Antila, Hanna, Kwak, Iris, Choi, Ashley, Pisciotti, Alexa, Covarrubias, Ivan, Baik, Justin, Eisch, Amelia, Beier, Kevin, Thomas, Steven, Weber, Franz, Chung, Shinjae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659376/
https://www.ncbi.nlm.nih.gov/pubmed/36331996
http://dx.doi.org/10.1073/pnas.2123528119
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author Antila, Hanna
Kwak, Iris
Choi, Ashley
Pisciotti, Alexa
Covarrubias, Ivan
Baik, Justin
Eisch, Amelia
Beier, Kevin
Thomas, Steven
Weber, Franz
Chung, Shinjae
author_facet Antila, Hanna
Kwak, Iris
Choi, Ashley
Pisciotti, Alexa
Covarrubias, Ivan
Baik, Justin
Eisch, Amelia
Beier, Kevin
Thomas, Steven
Weber, Franz
Chung, Shinjae
author_sort Antila, Hanna
collection PubMed
description In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupts sleep by increasing brief arousals (microarousals [MAs]), reducing sleep spindles, and impairing infraslow oscillations in the spindle band of the electroencephalogram during NREMs, while reducing REMs. This poor sleep quality was reflected in an increased number of calcium transients in the activity of noradrenergic (NE) neurons in the locus coeruleus (LC) during NREMs. Opto- and chemogenetic LC-NE activation in naïve mice is sufficient to change the sleep microarchitecture similar to stress. Conversely, chemogenetically inhibiting LC-NE neurons reduced MAs during NREMs and normalized their number after stress. Specifically inhibiting LC-NE neurons projecting to the preoptic area of the hypothalamus (POA) decreased MAs and enhanced spindles and REMs after stress. Optrode recordings revealed that stimulating LC-NE fibers in the POA indeed suppressed the spiking activity of POA neurons that are activated during sleep spindles and REMs and inactivated during MAs. Our findings reveal that changes in the dynamics of the stress-regulatory LC-NE neurons during sleep negatively affect sleep quality, partially through their interaction with the POA.
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spelling pubmed-96593762023-05-04 A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances Antila, Hanna Kwak, Iris Choi, Ashley Pisciotti, Alexa Covarrubias, Ivan Baik, Justin Eisch, Amelia Beier, Kevin Thomas, Steven Weber, Franz Chung, Shinjae Proc Natl Acad Sci U S A Biological Sciences In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupts sleep by increasing brief arousals (microarousals [MAs]), reducing sleep spindles, and impairing infraslow oscillations in the spindle band of the electroencephalogram during NREMs, while reducing REMs. This poor sleep quality was reflected in an increased number of calcium transients in the activity of noradrenergic (NE) neurons in the locus coeruleus (LC) during NREMs. Opto- and chemogenetic LC-NE activation in naïve mice is sufficient to change the sleep microarchitecture similar to stress. Conversely, chemogenetically inhibiting LC-NE neurons reduced MAs during NREMs and normalized their number after stress. Specifically inhibiting LC-NE neurons projecting to the preoptic area of the hypothalamus (POA) decreased MAs and enhanced spindles and REMs after stress. Optrode recordings revealed that stimulating LC-NE fibers in the POA indeed suppressed the spiking activity of POA neurons that are activated during sleep spindles and REMs and inactivated during MAs. Our findings reveal that changes in the dynamics of the stress-regulatory LC-NE neurons during sleep negatively affect sleep quality, partially through their interaction with the POA. National Academy of Sciences 2022-11-04 2022-11-08 /pmc/articles/PMC9659376/ /pubmed/36331996 http://dx.doi.org/10.1073/pnas.2123528119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Antila, Hanna
Kwak, Iris
Choi, Ashley
Pisciotti, Alexa
Covarrubias, Ivan
Baik, Justin
Eisch, Amelia
Beier, Kevin
Thomas, Steven
Weber, Franz
Chung, Shinjae
A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
title A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
title_full A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
title_fullStr A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
title_full_unstemmed A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
title_short A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
title_sort noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659376/
https://www.ncbi.nlm.nih.gov/pubmed/36331996
http://dx.doi.org/10.1073/pnas.2123528119
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