Research on the role of the POA GABAergic neuron in the sleep regulation.

• Project/Area Number: 24700322
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience in general
• Research Institution: University of Tsukuba (2013); Kanazawa University (2012)
• Principal Investigator: KANDA Natsuko 筑波大学, 国際統合睡眠医科学研究機構, 助教 (40432166)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: sleep / GABAergic neuron / preoptic area / orexin / channelrhodopsin / DREADD / hM3Dq / hM4Di

Research Abstract

GABAergic neurons in the preoptic area (POA) is thought to have a important role in sleep regulation. We applied DREADD system to POA GABAergic neurons to modulate activities of the neurons. Activation of POA GABAergic neurons increased total NREM sleep time. Inhibition of the neurons reduced REM sleep time and increased NREM sleep time during light period and reduced episode durations of wakefulness during dark period.
Axonal projections of POA GABAergic neurons were observed in hypothalamic area where orexin neurons localized using Channelrhodopsin2 (ChR2)as an anterograde tracer. Moreover, light stimulation of axonal terminals of POA GABAergic neuron which expressed ChR2 inhibited firings of orexin neurons in slice preparation. These results suggest that the functional connection between POA GABAergic neurons and orexin neurons might be an important pathway in sleep regulation.

Research Products

• [Journal Article] Effects of a newly developed potent orexin-2 receptor-selective antagonist, compound 1 m, on sleep/wakefulness states in mice. (2014)
  • Author(s): Etori K, Saito YC, Tsujino N, Sakurai T.
  • Journal Title: Frontiers in Neuroscience Volume: 8:8
  • DOI: 10.3389/fnins.2014.00008
  • NAID: 120005452005
  • Peer Reviewed
• [Journal Article] GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons. (2013)
  • Author(s): Saito YC, Tsujino N, Hasegawa E, Akashi K, Abe M, Mieda M, Sakimura K, Sakurai T.
  • Journal Title: Front Neural Circuits. Volume: 7 Pages: 192-192
  • DOI: 10.3389/fncir.2013.00192
  • Peer Reviewed
• [Journal Article] Chronic alterations in monoaminergic cells in the locus coeruleus in orexin neuron-ablated narcoleptic mice (2013)
  • Author(s): Tsujino N, Tsunematsu T,Uchigashima M, Konno K,Yamanaka A, Kobayashi K, Watanabe M, Koyama Y, Sakurai T
  • Journal Title: PLoS ONE Volume: 8 Issue: 7 Pages: e70012-e70012
  • DOI: 10.1371/journal.pone.0070012
  • NAID: 120005328803
  • Peer Reviewed
• [Journal Article] Differential roles of orexin receptors in the regulation of sleep/wakefulness (2013)
  • Author(s): Mieda M, Tsujino N, Sakurai T.
  • Journal Title: Front Endocrinol Volume: 4 Pages: 57-57
  • DOI: 10.3389/fendo.2013.00057
  • Peer Reviewed
• [Journal Article] Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness States. (2013)
  • Author(s): Furutani N, Hondo M, Kageyama H, Tsujino N, Mieda M, Yanagisawa M, Shioda S, Sakurai T.
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e62391-e62391
  • DOI: 10.1371/journal.pone.0062391
  • Peer Reviewed
• [Journal Article] Role of orexin in modulating arousal, feeding, and motivation. (2013)
  • Author(s): Tsujino N, Sakurai T
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 7:28 Pages: 28-28
  • DOI: 10.3389/fnbeh.2013.00028
  • Peer Reviewed
• [Journal Article] A Single Nucleotide Polymorphism of the Neuropeptide B/W receptor-1 Gene Influences the Evaluation of Facial Expressions (2012)
  • Author(s): Watanabe, N., Wada, M., Irukayama-Tomobe, Y., Ogata, Y., Tsujino, N., Suzuki,M., Furutani,N., Sakurai, T, Yamamoto, M
  • Journal Title: PLoS ONE Volume: 7(4) Issue: 4 Pages: e35390-e35390
  • DOI: 10.1371/journal.pone.0035390
  • Peer Reviewed
• [Journal Article] Circadian rhythm of leptin, orexin and ghrelin (2012)
  • Author(s): Tsujino N, Sakurai T
  • Journal Title: Nihon Rinsho Volume: 70(7) Pages: 1121-1125
  • NAID: 40019360318
• [Journal Article] レプチン、オレキシン、グレリンの日内リズムとその生理的意義
  • Author(s): 辻野なつ子、桜井武
  • Journal Title: 日本臨床 Volume: 2012年7月号特集
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22844792
• [Presentation] A critical role of serotonergic inhibitory projections to orexin neurons in regulation of sleep/wakefulness states (2013)
  • Author(s): 辻野なつ子、齊藤夕貴、本堂茉莉、阿部学、﨑村建司、櫻井武
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] Functional connection between GABAergic neurons in the preoptic area and orexinergic neurons in the hypothalamus (2013)
  • Author(s): 上田(辻野)なつ子、齊藤夕貴、阿部学、崎村建司、柳沢正史、桜井武
  • Organizer: 第51回日本生物物理学会年会
  • Place of Presentation: 国立京都国際会館発表10月29日ポスター
• [Presentation] Functional connection between GABAergic neurons in the preoptic area and orexinergic neurons in the hypothalamus. (2013)
  • Author(s): 上田（辻野）なつ子、齊藤夕貴、阿部学、崎村建司、柳沢正史、桜井武
  • Organizer: 第51回日本生物物理学会年会
  • Place of Presentation: 国立京都国際会館
• [Presentation] A critical role of serotonergic inhibitory projections to orexin neurons in regulation of sleep/wakefulness states. (2013)
  • Author(s): 辻野なつ子、齊藤夕貴、本堂茉莉、阿部学、﨑村建司、櫻井武
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀（東京）
• [Presentation] Chronic functional alterations of locus ceruleus noradrenergic neurons in orexin neuron-ablated narcoleptic mice (2012)
  • Author(s): Tsujino N, Tsunematsu T, Yamanaka A, Koyama Y, Sakurai T.
  • Organizer: European Sleep Research Society 2012
  • Place of Presentation: Paris, France
• [Presentation] Chronic functional alterations of locus ceruleus noradrenergic neurons in orexin neuron-ablated narcoleptic mice. (2012)
  • Author(s): Tsujino N, Tsunematsu T, Yamanaka A, Koyama Y, Sakurai T.
  • Organizer: European Sleep Research Society
  • Place of Presentation: CNIT (France)