Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneou...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chang-Rui Chen, Yu-Heng Zhong, Shan Jiang, Wei Xu, Lei Xiao, Zan Wang, Wei-Min Qu, Zhi-Li Huang
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	hypersomnolence disorder paraventricular hypothalamic nucleus chemogenetics optogenetics wakefulness Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/744e38fb596a477e82effaa63f65d63b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:744e38fb596a477e82effaa63f65d63b
record_format	dspace
spelling	oai:doaj.org-article:744e38fb596a477e82effaa63f65d63b2021-11-30T16:10:06ZDysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice10.7554/eLife.699092050-084Xe69909https://doaj.org/article/744e38fb596a477e82effaa63f65d63b2021-11-01T00:00:00Zhttps://elifesciences.org/articles/69909https://doaj.org/toc/2050-084XHypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 hr, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.Chang-Rui ChenYu-Heng ZhongShan JiangWei XuLei XiaoZan WangWei-Min QuZhi-Li HuangeLife Sciences Publications Ltdarticlehypersomnolence disorderparaventricular hypothalamic nucleuschemogeneticsoptogeneticswakefulnessMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypersomnolence disorder paraventricular hypothalamic nucleus chemogenetics optogenetics wakefulness Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	hypersomnolence disorder paraventricular hypothalamic nucleus chemogenetics optogenetics wakefulness Medicine R Science Q Biology (General) QH301-705.5 Chang-Rui Chen Yu-Heng Zhong Shan Jiang Wei Xu Lei Xiao Zan Wang Wei-Min Qu Zhi-Li Huang Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
description	Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 hr, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.
format	article
author	Chang-Rui Chen Yu-Heng Zhong Shan Jiang Wei Xu Lei Xiao Zan Wang Wei-Min Qu Zhi-Li Huang
author_facet	Chang-Rui Chen Yu-Heng Zhong Shan Jiang Wei Xu Lei Xiao Zan Wang Wei-Min Qu Zhi-Li Huang
author_sort	Chang-Rui Chen
title	Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
title_short	Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
title_full	Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
title_fullStr	Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
title_full_unstemmed	Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
title_sort	dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/744e38fb596a477e82effaa63f65d63b
work_keys_str_mv	AT changruichen dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT yuhengzhong dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT shanjiang dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT weixu dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT leixiao dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT zanwang dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT weiminqu dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice AT zhilihuang dysfunctionsoftheparaventricularhypothalamicnucleusinducehypersomniainmice
_version_	1718406450580029440

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

Ejemplares similares