Hypocretin in locus coeruleus and dorsal raphe nucleus mediates inescapable footshock stimulation (IFS)-induced REM sleep alteration

Sleep

article

Lo, Yun¹  Yi, Pei-Lu²  Hsiao, Yi-Tse¹  Chang, Fang-Chia¹ 

[1] Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University;Department of Sport Management, College of Tourism, Leisure and Sports, Aletheia University;Graduate Institute of Brain & Mind Sciences, College of Medicine, National Taiwan University;Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University;Department of Medicine, College of Medicine, China Medical University

关键词: dorsal raphe nucleus;    hypocretin;    inescapable footshock stimulation (IFS);    lateral hypothalamus;    locus coeruleus;    REM sleep;   

DOI  :  10.1093/sleep/zsab301

学科分类：生理学

来源: American Academy of Sleep Medicine

【 摘 要 】

Hypocretin (hcrt) is a stress-reacting neuropeptide mediating arousal and energy homeostasis. An inescapable footshock stimulation (IFS) could initiate the hcrt release from the lateral hypothalamus (LHA) and suppresses rapid eye movement (REM) sleep in rodents. However, the effects of the IFS-induced hcrts on REM-off nuclei, the locus coeruleus (LC) and dorsal raphe nucleus (DRN), remained unclear. We hypothesized that the hcrt projections from the LHA to LC or DRN mediate IFS-induced sleep disruption. Our results demonstrated that the IFS increased hcrt expression and the neuronal activities in the LHA, hypothalamus, brainstem, thalamus, and amygdala. Suppressions of REM sleep and slow wave activity during non-REM (NREM) sleep caused by the high expression of hcrts were blocked when a nonspecific and dual hcrt receptor antagonist was administered into the LC or DRN. Furthermore, the IFS also caused an elevated innate anxiety, but was limitedly influenced by the hcrt antagonist. This result suggests that the increased hcrt concentrations in the LC and DRN mediate stress-induced sleep disruptions and might partially involve IFS-induced anxiety.

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