Serotonergic integration of circadian clock and ultradian sleep-wake cycles

• Project/Area Number: 24621012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 睡眠科学
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MIYAMOTO Hiroyuki 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (90312280)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: サーカディアンリズム / 睡眠・覚醒 / セロトニン / 視交叉上核 / 前脳基底部・視索前野 / 神経活動 / セロトニン系 / 前納基底部・視索前野 / 睡眠障害 / Local Field Potential

Outline of Final Research Achievements

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus generates a 24 h rhythm of sleep and arousal. While neuronal spiking activity in the SCN provides a functional circadian oscillator that propagates throughout the brain, the ultradian sleep-wake state is regulated by the basal forebrain/preoptic area (BF/POA). How this SCN circadian oscillation is integrated into the shorter sleep-wake cycles remains unclear. We examined the temporal patterns of neuronal activity in these key brain regions in behaving rats. We identified a diurnal rhythm in the BF/POA that was selectively degraded when diurnal arousal patterns were disrupted by acute brain serotonin depletion despite robust circadian spiking activity in the SCN. Local blockade of serotonergic transmission in the BF/POA was sufficient to disrupt the diurnal sleep-wake rhythm of mice. These results suggest that the serotonergic system enables the BF/POA to couple the SCN circadian signal to ultradian sleep-wake cycles.

Research Products

• [Journal Article] Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures. (2014)
  • Author(s): Naoko H. Tomioka, Hiroki Yasuda, Hiroyuki Miyamoto, Minoru Hatayama, Naoko Morimura, Yoshifumi Matsumoto, Toshimitsu Suzuki, Maya Odagawa, Yuri S. Odaka, Yoshimi Iwayama, Ji Won Um, Jaewon Ko, Yushi Inoue, Sunao Kaneko, Shinichi Hirose, Kazuyuki Yamada, Takeo Yoshikawa, Kazuhiro Yamakawa, Jun Aruga
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 45011-16
  • DOI: 10.1038/ncomms5501
  • Peer Reviewed / Open Access
• [Journal Article] IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice. (2013)
  • Author(s): Hisatsune C, Miyamoto H, Hirono M, Yamaguchi N, Sugawara T, Ogawa N, Ebisui E, Ohshima T, Yamada M, Hensch TK, Hattori M, Mikoshiba K.
  • Journal Title: Front Neural Circuits. Volume: ７ Pages: 156-156
  • DOI: 10.3389/fncir.2013.00156
  • Peer Reviewed
• [Journal Article] A theory of the transition to critical period plasticity: inhibition selectively suppresses spontaneous activity. (2013)
  • Author(s): Toyoizumi T, Miyamoto H, Yazaki-Sugiyama Y, Atapour N, Hensch TK, Miller KD.
  • Journal Title: Neuron Volume: 80 Issue: 1 Pages: 51-63
  • DOI: 10.1016/j.neuron.2013.07.022
  • Peer Reviewed
• [Journal Article] Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome. (2013)
  • Author(s): Ogiwara I, Iwasato T, Miyamoto H, Iwata R, Yamagata T, Mazaki E, Yanagawa Y, Tamamaki N, Hensch TK, Itohara S, Yamakawa K.
  • Journal Title: Hum Mol Genet. Volume: 22 Issue: 23 Pages: 4784-4804
  • DOI: 10.1093/hmg/ddt331
  • Peer Reviewed
• [Journal Article] Serotonergic integration of circadian clock and ultradian sleep-wake cycles (2012)
  • Author(s): Miyamoto H, Nakamaru-Ogiso E, Hamada K, Hensch TK.
  • Journal Title: The Journal of Neuroscience Volume: 32 Issue: 42 Pages: 14794-14803
  • DOI: 10.1523/jneurosci.0793-12.2012
  • Peer Reviewed
• [Journal Article] Nakamaru-Ogiso E, Miyamoto H, Hamada K, Tsukada K, Takai K. (2012)
  • Author(s): Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep-wake cycles.
  • Journal Title: European Journal of Neuroscience Volume: 35 Issue: 11 Pages: 1762-11770
  • DOI: 10.1111/j.1460-9568.2012.08077.x
  • Peer Reviewed
• [Journal Article] Mouse with Na(v)1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment. (2012)
  • Author(s): Ito S, Ogiwara I, Yamada K, Miyamoto H, Hensch TK, Osawa M, Yamakawa K.
  • Journal Title: Neurobiology of Disease Volume: 49C Pages: 29-40
  • DOI: 10.1016/j.nbd.2012.08.003
  • Peer Reviewed
• [Journal Article] Selective control of inhibitory synapse development by Slitrk3-PTPδ trans-synaptic interaction (2012)
  • Author(s): Hideto Takahashi, Kei-ichi Katayama, Kazuhiro Sohya, Hiroyuki Miyamoto, Tuhina Prasad, Yoshifumi Matsumoto, Maya Ota, Hiroki Yasuda, Tadaharu Tsumoto, Jun Aruga, Ann Marie Craig
  • Journal Title: Nature Neuroscience Volume: 15 Issue: 3 Pages: 389-398
  • DOI: 10.1038/nn.3040
  • Peer Reviewed
• [Presentation] 睡眠による視覚野機能的神経結合の促進と抑制性制御 (2014)
  • Author(s): 宮本浩行、槌本佳子、ヘンシュ貴雄
  • Organizer: 第18回視覚科学フォーラム 特別企画シンポジウム
  • Place of Presentation: 前橋工科大学 （群馬県 前橋市）
  • Year and Date: 2014-08-18 – 2014-08-19
  • Invited
• [Presentation] Sleep strengthens local cortical connectivity through inhibition (2013)
  • Author(s): Miyamoto H, Hensch TK
  • Organizer: 35th Annual International Conference of the IEEE engineering in Medicine and Biological Society
  • Place of Presentation: 大阪市
  • Invited
• [Presentation] セロトニン系によって統合されるサーカディアン生物時計と睡眠・覚醒 (2013)
  • Author(s): 宮本浩行
  • Organizer: 日本睡眠学会大38回定期学術集会
  • Place of Presentation: 秋田市
  • Invited
• [Presentation] An essential role of Elfn1 in the formation of hippocampal inhibitory neural circuits containing somatostatin-positive neurons (2013)
  • Author(s): Tomioka NH, Miyamoto H, Hatayama M, , Morimura N, Matsumoto Y, Suzuki T, Odagawa MO, Odaka YS, Iwayama Y, Yamada K, Yoshikawa T, Yamakawa K, Aruga J
  • Organizer: Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] Nav1.1 haploinsufficient excitatory and inhibitory neurons play distinct roles in the epileptic pathology in Dravet syndrome model mice. (2013)
  • Author(s): Ogiwara I, Iwasato T, Miyamoto H, Iwata R, Yamagata T, Mazaki E, Yanagawa Y, Tamamaki N, Hensch TK, Itohara S, Yamakawa K
  • Organizer: Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] セロトニン系によって統合されるサーカディアン振動体と睡眠・覚醒交替 (2012)
  • Author(s): 宮本浩行
  • Organizer: 日本睡眠学会第37回定期学術集会
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] セロトニンによって束ねられる睡眠・覚醒と24時間リズム (2012)
  • Author(s): 宮本浩行
  • Organizer: さきがけ 「脳神経回路の形成・動作と制御」領域 研究成果報告会
  • Place of Presentation: 名古屋市
  • Invited
• [Presentation] Increased seizure-susceptibility is caused by loss of Elfn1, an interneuron-specific LRR transmembrane protein (2012)
  • Author(s): Tomioka NH, Miyamoto H, Odagawa M, Odaka YS, Hatayama M, Morimura N, MatsumotoY, Yamada K, Aruga J
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡市
  • Invited
• [Presentation] 興奮と抑制信号を介した、睡眠による機能的結合の促進 (2012)
  • Author(s): 宮本浩行、ヘンシュ貴雄
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋市
• [Presentation] パルブアルブミン陽性介在性神経細胞特異的Scn1a遺伝子破壊によるてんかんモデルマウスの樹立 (2012)
  • Author(s): 荻原 郁夫 宮本 浩行 眞崎 恵美 玉巻 伸章 ヘンシュ 貴雄、山川 和弘
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋市
• [Presentation] Selective deletion of the Scn1a gene encoding voltage-gated sodium channel α1 in parvalbumin positive cells in mice triggers epileptic seizures (2012)
  • Author(s): 荻原 郁夫 宮本 浩行 眞崎 恵美 玉巻 伸章 ヘンシュ 貴雄、山川 和弘
  • Organizer: 第46回日本てんかん学会
  • Place of Presentation: 東京都
• [Remarks] 睡眠・覚醒機能と24時間リズムをセロトニンが束ねる－睡眠・覚醒のサーカディアンリズム形成機構－
  • URL: http://www.riken.jp/pr/press/2012/20121017/
• [Remarks] 研究の紹介
  • URL: http://miyamotosleep.web.fc2.com/
• [Remarks] 脳発達過程における「臨界期」開始の新理論を提唱
  • URL: http://www.riken.jp/pr/press/2013/20131003_1/
• [Remarks] 難治性障害「ジストニア」の発症メカニズムに新たな知見
  • URL: http://www.riken.jp/pr/press/2013/20130913_1/
• [Remarks] 乳児難治てんかんの突然死抑制効果の発見 -興奮性神経細胞ナトリウムチャネル発現低下が鍵-
  • URL: http://www.riken.jp/pr/press/2013/20130807_1/
• [Remarks] 睡眠・覚醒機能と24時間リズムをセロトニンが束ねる
  • URL: http://www.riken.go.jp/pr/press/2012/20121017/
• [Remarks] ー研究の紹介ー 宮本浩行
  • URL: http://miyamotosleep.web.fc2.com
• [Remarks] てんかんモデルマウスで自閉症に似た社会性低下と記憶学習障害を発見
  • URL: http://www.riken.go.jp/pr/press/2012/20120927_2/
• [Remarks] 抑制性シナプス形成に重要なタンパク質を発見－脳機能における抑制性シナプスの役割解明に手掛かり－
  • URL: http://www.riken.go.jp/pr/press/2012/20120130/