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Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear

INTRODUCTION: Fear and sleep impairments common co-exist, but the underlying mechanisms remain unclear. Hypothalamic orexinergic neurons are involved in the regulation of sleep-wake and fear expression. The ventrolateral preoptic area (VLPO) is an essential brain region to promote sleep, and orexine...

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Autores principales: Ma, Caifen, Zhou, Ning, Ma, Kang, Niu, Jiandong, Mi, Ting, He, Zhenquan, Wen, Yujun, Liu, Chunhong, He, Zhongyi, Niu, Jianguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043189/
https://www.ncbi.nlm.nih.gov/pubmed/36998723
http://dx.doi.org/10.3389/fnins.2023.1122803
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author Ma, Caifen
Zhou, Ning
Ma, Kang
Niu, Jiandong
Mi, Ting
He, Zhenquan
Wen, Yujun
Liu, Chunhong
He, Zhongyi
Niu, Jianguo
author_facet Ma, Caifen
Zhou, Ning
Ma, Kang
Niu, Jiandong
Mi, Ting
He, Zhenquan
Wen, Yujun
Liu, Chunhong
He, Zhongyi
Niu, Jianguo
author_sort Ma, Caifen
collection PubMed
description INTRODUCTION: Fear and sleep impairments common co-exist, but the underlying mechanisms remain unclear. Hypothalamic orexinergic neurons are involved in the regulation of sleep-wake and fear expression. The ventrolateral preoptic area (VLPO) is an essential brain region to promote sleep, and orexinergic axonal fibers projecting to the VLPO are involved in the maintenance of sleep-wake. Neural pathways from hypothalamic orexin neurons to the VLPO might mediate sleep impairments induced by conditioned fear. METHODS: To verify above hypothesis, electroencephalogram (EEG) and electromyogram (EMG) were recorded for analysis of sleep-wake states before and 24 h after conditioned fear training. The retrograde tracing technique and immunofluorescence staining was used to identify the projections from the hypothalamic orexin neurons to the VLPO and to observe their activation in mice with conditioned fear. Moreover, optogenetic activation or inhibition of hypothalamic orexin-VLPO pathways was performed to observe whether the sleep-wake can be regulated in mice with conditioned fear. Finally, orexin-A and orexin receptor antagonist was administered into the VLPO to certify the function of hypothalamic orexin-VLPO pathways on mediating sleep impairments induced by conditioned fear. RESULTS: It was found that there was a significant decrease in the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep time and a significant increase in the wakefulness time in mice with conditioned fear. The results of retrograde tracing technique and immunofluorescence staining showed that hypothalamic orexin neurons projected to the VLPO and observed the CTB labeled orexin neurons were significantly activated (c-Fos+) in the hypothalamus in mice with conditioned fear. Optogenetic activation of hypothalamic orexin to the VLPO neural pathways significantly decreased NREM and REM sleep time and increased wakefulness time in mice with conditioned fear. A significant decrease in NREM and REM sleep time and an increase in wakefulness time were observed after the injection of orexin-A into the VLPO, and the effects of orexin-A in the VLPO were blocked by a pre-administrated dual orexin antagonist (DORA). CONCLUSION: These findings suggest that the neural pathways from hypothalamic orexinergic neurons to the VLPO mediate sleep impairments induced by conditioned fear.
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spelling pubmed-100431892023-03-29 Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear Ma, Caifen Zhou, Ning Ma, Kang Niu, Jiandong Mi, Ting He, Zhenquan Wen, Yujun Liu, Chunhong He, Zhongyi Niu, Jianguo Front Neurosci Neuroscience INTRODUCTION: Fear and sleep impairments common co-exist, but the underlying mechanisms remain unclear. Hypothalamic orexinergic neurons are involved in the regulation of sleep-wake and fear expression. The ventrolateral preoptic area (VLPO) is an essential brain region to promote sleep, and orexinergic axonal fibers projecting to the VLPO are involved in the maintenance of sleep-wake. Neural pathways from hypothalamic orexin neurons to the VLPO might mediate sleep impairments induced by conditioned fear. METHODS: To verify above hypothesis, electroencephalogram (EEG) and electromyogram (EMG) were recorded for analysis of sleep-wake states before and 24 h after conditioned fear training. The retrograde tracing technique and immunofluorescence staining was used to identify the projections from the hypothalamic orexin neurons to the VLPO and to observe their activation in mice with conditioned fear. Moreover, optogenetic activation or inhibition of hypothalamic orexin-VLPO pathways was performed to observe whether the sleep-wake can be regulated in mice with conditioned fear. Finally, orexin-A and orexin receptor antagonist was administered into the VLPO to certify the function of hypothalamic orexin-VLPO pathways on mediating sleep impairments induced by conditioned fear. RESULTS: It was found that there was a significant decrease in the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep time and a significant increase in the wakefulness time in mice with conditioned fear. The results of retrograde tracing technique and immunofluorescence staining showed that hypothalamic orexin neurons projected to the VLPO and observed the CTB labeled orexin neurons were significantly activated (c-Fos+) in the hypothalamus in mice with conditioned fear. Optogenetic activation of hypothalamic orexin to the VLPO neural pathways significantly decreased NREM and REM sleep time and increased wakefulness time in mice with conditioned fear. A significant decrease in NREM and REM sleep time and an increase in wakefulness time were observed after the injection of orexin-A into the VLPO, and the effects of orexin-A in the VLPO were blocked by a pre-administrated dual orexin antagonist (DORA). CONCLUSION: These findings suggest that the neural pathways from hypothalamic orexinergic neurons to the VLPO mediate sleep impairments induced by conditioned fear. Frontiers Media S.A. 2023-03-14 /pmc/articles/PMC10043189/ /pubmed/36998723 http://dx.doi.org/10.3389/fnins.2023.1122803 Text en Copyright © 2023 Ma, Zhou, Ma, Niu, Mi, He, Wen, Liu, He and Niu. https://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) and the copyright owner(s) 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
Ma, Caifen
Zhou, Ning
Ma, Kang
Niu, Jiandong
Mi, Ting
He, Zhenquan
Wen, Yujun
Liu, Chunhong
He, Zhongyi
Niu, Jianguo
Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
title Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
title_full Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
title_fullStr Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
title_full_unstemmed Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
title_short Neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
title_sort neural pathways from hypothalamic orexin neurons to the ventrolateral preoptic area mediate sleep impairments induced by conditioned fear
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043189/
https://www.ncbi.nlm.nih.gov/pubmed/36998723
http://dx.doi.org/10.3389/fnins.2023.1122803
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