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Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation.
J Neurosci 2014; 34(20):6896-909JN

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system. The activity of these cells was controlled by optogenetics by expressing channelrhodopsin2 (E123T/T159C) or archaerhodopsin-T in MCH neurons. Acute optogenetic activation of MCH neurons at 10 Hz induced transitions from non-REM (NREM) to REM sleep and increased REM sleep time in conjunction with decreased NREM sleep. Activation of MCH neurons while mice were in NREM sleep induced REM sleep, but activation during wakefulness was ineffective. Acute optogenetic silencing of MCH neurons using archaerhodopsin-T had no effect on any vigilance states. Temporally controlled ablation of MCH neurons by cell-specific expression of diphtheria toxin A increased wakefulness and decreased NREM sleep duration without affecting REM sleep. Together, these results indicate that acute activation of MCH neurons is sufficient, but not necessary, to trigger the transition from NREM to REM sleep and that MCH neurons also play a role in the initiation and maintenance of NREM sleep.

Authors+Show Affiliations

Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan, The Japan Society for the Promotion of Sciences, Tokyo 102-8472, Japan.Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan, The Japan Society for the Promotion of Sciences, Tokyo 102-8472, Japan, Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8787, Japan.Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160-8582, Japan.Research Institute for Microbial Disease, Osaka University, Suita 565-0781 Japan, and.Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California 94025.Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan, yamank@riem.nagoya-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24828644

Citation

Tsunematsu, Tomomi, et al. "Optogenetic Manipulation of Activity and Temporally Controlled Cell-specific Ablation Reveal a Role for MCH Neurons in Sleep/wake Regulation." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 34, no. 20, 2014, pp. 6896-909.
Tsunematsu T, Ueno T, Tabuchi S, et al. Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. J Neurosci. 2014;34(20):6896-909.
Tsunematsu, T., Ueno, T., Tabuchi, S., Inutsuka, A., Tanaka, K. F., Hasuwa, H., ... Yamanaka, A. (2014). Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 34(20), pp. 6896-909. doi:10.1523/JNEUROSCI.5344-13.2014.
Tsunematsu T, et al. Optogenetic Manipulation of Activity and Temporally Controlled Cell-specific Ablation Reveal a Role for MCH Neurons in Sleep/wake Regulation. J Neurosci. 2014 May 14;34(20):6896-909. PubMed PMID: 24828644.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. AU - Tsunematsu,Tomomi, AU - Ueno,Takafumi, AU - Tabuchi,Sawako, AU - Inutsuka,Ayumu, AU - Tanaka,Kenji F, AU - Hasuwa,Hidetoshi, AU - Kilduff,Thomas S, AU - Terao,Akira, AU - Yamanaka,Akihiro, PY - 2014/5/16/entrez PY - 2014/5/16/pubmed PY - 2014/7/11/medline KW - REM sleep KW - ablation KW - cell fate KW - channelrhodopsin2 KW - hypothalamus KW - optogenetics SP - 6896 EP - 909 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 34 IS - 20 N2 - Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system. The activity of these cells was controlled by optogenetics by expressing channelrhodopsin2 (E123T/T159C) or archaerhodopsin-T in MCH neurons. Acute optogenetic activation of MCH neurons at 10 Hz induced transitions from non-REM (NREM) to REM sleep and increased REM sleep time in conjunction with decreased NREM sleep. Activation of MCH neurons while mice were in NREM sleep induced REM sleep, but activation during wakefulness was ineffective. Acute optogenetic silencing of MCH neurons using archaerhodopsin-T had no effect on any vigilance states. Temporally controlled ablation of MCH neurons by cell-specific expression of diphtheria toxin A increased wakefulness and decreased NREM sleep duration without affecting REM sleep. Together, these results indicate that acute activation of MCH neurons is sufficient, but not necessary, to trigger the transition from NREM to REM sleep and that MCH neurons also play a role in the initiation and maintenance of NREM sleep. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/24828644/Optogenetic_manipulation_of_activity_and_temporally_controlled_cell_specific_ablation_reveal_a_role_for_MCH_neurons_in_sleep/wake_regulation_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=24828644 DB - PRIME DP - Unbound Medicine ER -