皮質抑制性神経細胞が備える、特異的シナプス結合則の解明

• Project Area: Neural Diversity and Neocortical Organization
• Project/Area Number: 25123709
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: 日置 寛之 京都大学, 医学(系)研究科(研究院), 助教 (00402850)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 大脳新皮質 / 抑制性神経細胞 / シナプス結合 / 遺伝子改変マウス / ウイルスベクター

Outline of Annual Research Achievements

高次機能発現において、大脳新皮質が最も重要な役割を果たすことは、多くの研究者が認めるところであろう。しかし、その構造的基盤である局所神経回路、そしてその形成メカニズムについては、未だ解析が進んでいないのが現状である。本研究課題では、parvalbumin（PV）発現抑制性神経細胞に焦点を当て、抑制性神経細胞が備えるシナプス結合様式のルール、および特異的シナプス結合を形成・維持するメカニズムの解明を目指している。
(1) 皮質抑制性神経細胞が構成するネットワーク構造の解析
申請者らが開発してきた遺伝子改変マウス（PV発現細胞をゴルジ染色様に標識）、Jackson labから入手したCre発現マウス（PV-Cre, SOM-Cre, VIP-Cre）、そして各種ウイルスベクター（レンチウイルス、アデノ随伴ウイルスなど）を用い、各種抑制性神経細胞間のシナプス結合様式を定量的解析を進めてきた。先行研究において、PV発現細胞への入力特性を第一次体性感覚野（S1）で検討したところ、細胞体と樹状突起という2つのコンパートメントにおいて、抑制性入力様式が異なることを見出した。第一次運動野（M1）においても同様の解析を進めたところ、S1とM1には共通な結合様式が認められる一方で、領野特異的なシナプス結合も存在することが分かった。論文発表に向け、引き続き追加実験を進めているところである。
(2) 抑制性神経回路の形成・維持メカニズムの解明
特異的結合を形成・維持するためには、プレ・ポスト間で何らかの相互作用が必要であると想定するのが妥当である。関連遺伝子の時空間パターンを検討する目的で、予備実験を行った。また、生理学的手法による解析にも取り組むべく、セットアップの準備・予備実験を進めた。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Ventral medial nucleus neurons send thalamocortical afferents more widely and more preferentially to layer 1 than neurons of the ventral anterior-ventral lateral nuclear complex in the rat. (2015)
  • Author(s): Kuramoto E, Ohno S, Furuta T, Unzai T, Tanaka YR, Hioki H, Kaneko T.
  • Journal Title: Cereb Cortex Volume: 25 Issue: 1 Pages: 221-235
  • DOI: 10.1093/cercor/bht216
  • Peer Reviewed / Open Access
• [Journal Article] Efficient and graded gene expression in glia and neurons of primary cerebellar cultures transduced by lentiviral vectors. (2015)
  • Author(s): Kumar S, Zimmermann K, Hioki H, Pfeifer A, Baader SL.
  • Journal Title: Histochem Cell Biol Volume: 143(1) Issue: 1 Pages: 109-121
  • DOI: 10.1007/s00418-014-1260-8
  • Peer Reviewed / Open Access
• [Journal Article] Compartmental Organization of Synaptic Inputs to Parvalbumin-Expressing GABAergic Neurons in Mouse Primary Somatosensory Cortex. (2015)
  • Author(s): Hioki H
  • Journal Title: Anat Sci Int Volume: 90(1) Issue: 1 Pages: 7-21
  • DOI: 10.1007/s12565-014-0264-8
  • Peer Reviewed / Open Access
• [Journal Article] Structural basis for serotonergic regulation of neural circuits in the mouse olfactory bulb. (2015)
  • Author(s): Suzuki Y, Kiyokage E, Sohn J, Hioki H, Toida K.
  • Journal Title: The Journal of Comparative Neurology Volume: 523 Issue: 2 Pages: 262-80
  • DOI: 10.1002/cne.23680
  • Peer Reviewed / Open Access
• [Journal Article] Different Cortical Projections from Three Subdivisions of the Rat Lateral Posterior Thalamic Nucleus: A Single Neuron Tracing Study with Viral Vectors. (2015)
  • Author(s): Nakamura H, Hioki H, Furuta T, Kaneko T.
  • Journal Title: Eur J Neurosci Volume: In Press Issue: 10 Pages: 1-7
  • DOI: 10.1111/ejn.12882
  • NAID: 120005674600
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Convergence of Lemniscal and Local Excitatory Inputs on Large GABAergic Tectothalamic Neurons. (2015)
  • Author(s): Ito T, Hioki H, Sohn J, Okamoto S, Kaneko T, Iino S, Oliver DL.
  • Journal Title: J Comp Neurol Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sequence of molecular events during maturation of developing mouse prefrontal cortex. (2015)
  • Author(s): Ueda S, Niwa M, Hioki H, Sohn J, Kaneko T, Sawa A, Sakurai T.
  • Journal Title: Mol Neuropsychiatry Volume: press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ウイルスベクターを用いた遺伝子導入による単一ニューロン標識 (2015)
  • Author(s): 中村悠、日置寛之
  • Journal Title: 細胞 Volume: 47 Pages: 46-49
  • NAID: 40020490548
• [Journal Article] Unbalanced excitability underlies offline reactivation of behaviorally activated neurons. (2014)
  • Author(s): Mizunuma, M., Norimoto, H., Tao, K., Egawa, T., Hanaoka, K., Sakaguchi, T., Hioki, H., Kaneko, T., Yamaguchi, S., Nagano, T., Matsuki, N., Ikegaya, Y.
  • Journal Title: Nature Neuroscience Volume: 17 Issue: 4 Pages: 503-505
  • DOI: 10.1038/nn.3674
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preprodynorphin-Expressing Neurons Constitute a Large Subgroup of Somatostatin-Expressing GABAergic Interneurons in the Mouse Neocortex (2014)
  • Author(s): Jaerin Sohn, Hiroyuki Hioki, Shinichiro Okamoto, and Takeshi Kaneko
  • Journal Title: The Journal of Comparative Neurology Volume: 522 Issue: 7 Pages: 1506-1526
  • DOI: 10.1002/cne.23477
  • Peer Reviewed
• [Journal Article] Psychological Stress Activates a Dorsomedial Hypothalamus-Medullary Raphe Circuit Driving Brown Adipose Tissue Thermogenesis and Hyperthermia. (2014)
  • Author(s): Kataoka N, Hioki H, Kaneko T, Nakamura K.
  • Journal Title: Cell Metab Volume: 20(2) Issue: 2 Pages: 346-358
  • DOI: 10.1016/j.cmet.2014.05.018
  • NAID: 120005553940
  • Peer Reviewed
• [Journal Article] 3D Clustering of GABAergic Neurons Enhances Inhibitory Actions on Excitatory Neurons in the Mouse Visual Cortex. (2014)
  • Author(s): Ebina T, Sohya K, Imayoshi I, Yin ST, Kimura R, Yanagawa Y, Kameda H, Hioki H, Kaneko T, Tsumoto T.
  • Journal Title: Cell Rep Volume: 9(5) Issue: 5 Pages: 1896-1907
  • DOI: 10.1016/j.celrep.2014.10.057
  • Peer Reviewed
• [Journal Article] 抑制性インターニューロンとオシレーション (2014)
  • Author(s): 日置寛之
  • Journal Title: Clinical Neuroscience Volume: 32 Pages: 743-746
• [Journal Article] パルブアルブミン発現皮質抑制性神経細胞に対する、細胞種特異的シナプス入力様式の解明 (2014)
  • Author(s): 日置寛之
  • Journal Title: 解剖学雑誌 Volume: 89 Pages: 41-42
• [Journal Article] A drug screening platform for Alzheimer's disease with intracellular Aβ oligomers using patient-specific iPSCs (2013)
  • Author(s): Kondo, T., (他24名), Murakami, K., Irie, K., Klein, W. L., Mori, H., Asada, T., Takahashi, R., Iwata, N., Yamanaka, S., Inoue, H
  • Journal Title: Cell Stem Cell Volume: 12 Issue: 4 Pages: 487-496
  • DOI: 10.1016/j.stem.2013.01.009
  • Peer Reviewed / Open Access
• [Journal Article] EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDial and mDia3 in combination (2013)
  • Author(s): Yosuke Toyoda, Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Hiroshi Nishimaru, Hiroyuki Hioki, Takeshi Kaneko, Toshimasa Ishizaki, Tomoyuki Fnruyashiki and Shuh Narumiva
  • Journal Title: Genes to Cells Volume: 18 Issue: 10 Pages: 873-885
  • DOI: 10.1111/gtc.12081
  • Peer Reviewed
• [Journal Article] Differential expression of VGLUT1 or VGLUT2 in the trigeminothalamic or trigeminocerebellar projection neurons in the rat (2013)
  • Author(s): Ge S-N, Li Z-H, Tang J, Ma Y, Hioki H, Zhang T, Lu Y-C, Zhang F-X, Mizuno N, Kaneko T, Liu Y-Y, Lung MSY, Gao G-D,Li J-L
  • Journal Title: Brain Structure and Function Volume: (in press) Issue: 1 Pages: 211-229
  • DOI: 10.1007/s00429-012-0495-1
  • Peer Reviewed
• [Presentation] Compartmental organization of synaptic inputs to parvalbumin-expressing inhibitory neurons in mouse neocortex. (2015)
  • Author(s): 日置寛之
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
  • Invited
• [Presentation] Imaging and implications of dopaminergic neurons for movement disorder: "opposite sides of the same coin" in Parkinson's disease. (2015)
  • Author(s): 松田和郎、古田貴寛、中村公一、日置寛之、金子武嗣
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
  • Invited
• [Presentation] Excitatory and inhibitory inputs to vasoactive intestinal polypeptide-expressing neurons in the mouse primary somatosensory cortex. (2015)
  • Author(s): 孫在隣、日置寛之、岡本慎一郎、金子武嗣
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Maturation processes of developing prefrontal cortex of normal and disease model mice. (2015)
  • Author(s): 櫻井武、上田修平、丹羽美苗、日置寛之、孫在隣、金子武嗣、澤明
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 皮質抑制性神経細胞が備える普遍的・特異的シナプス結合則 (2015)
  • Author(s): 日置寛之
  • Organizer: 大阪大学歯学部・大学院歯学研究科 大学院特別講義
  • Place of Presentation: 吹田
  • Year and Date: 2015-01-30
  • Invited
• [Presentation] 大脳皮質における非カラム的局所回路の作動原理の究明 (2014)
  • Author(s): 日置寛之、金子武嗣
  • Organizer: 包括脳ネットワーク冬のワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2014-12-11 – 2014-12-13
  • Invited
• [Presentation] Gene expression profiles of developing prefrontal cortex of normal and disease model mice. (2014)
  • Author(s): Ueda S, Niwa M, Hioki H, Sohn J, Kaneko T, Sawa A, Sakurai T.
  • Organizer: 包括脳ネットワーク冬のワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2014-12-11 – 2014-12-13
• [Presentation] Three Types of Thalamocortical Projections of the Lateral Posterior Thalamic Nucleus in the Rat: A Single Neuron Tracing Study with Viral Vectors. (2014)
  • Author(s): Nakamura H, Hioki H, Furuta Y, Kaneko T.
  • Organizer: 包括脳ネットワーク冬のワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2014-12-11 – 2014-12-13
• [Presentation] Three Types of Thalamocortical Projections from the Rat Lateral Posterior Thalamic Nucleus: A Single Neuron-Tracing Study Using Viral Vectors. (2014)
  • Author(s): 中村悠、日置寛之、古田貴寛、金子武嗣
  • Organizer: 第90回日本解剖学会・近畿支部学術集会
  • Place of Presentation: 吹田
  • Year and Date: 2014-11-29
• [Presentation] Vesicular glutamate transporter 3 is essential for the proper development of central mechanical pain circuits. (2014)
  • Author(s): PEIRS C, WILLIAMS S-PG, WALSH CE, CAGLE NE, GOLDRING AC, HIOKI H, SEAL RP.
  • Organizer: The 44th Society for Neuroscience Annual Meeting
  • Place of Presentation: Washington
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] GABAergic interneurons form spatial clusters in the mouse visual cortex to enhance inhibitory actions on excitatory neurons. (2014)
  • Author(s): EBINA T, SOHYA K, IMAYOSHI I, YIN ST, KIMURA R, YANAGAWA Y, KAMEDA H, HIOKI H, KANEKO T, TSUMOTO T.
  • Organizer: The 44th Society for Neuroscience Annual Meeting
  • Place of Presentation: Washington
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Gene expression profiles of developing prefrontal cortex of normal and disease model mice. (2014)
  • Author(s): Ueda S, Niwa M, Hioki H, Sohn J, Kaneko T, Sawa A, Sakurai T.
  • Organizer: Axon Guidance, Synapse Formation and Regeneration 2014 (CSHL Meeting)
  • Place of Presentation: Cold Spring Harbor
  • Year and Date: 2014-09-16 – 2014-09-20
• [Presentation] Functional significance of GABAergic interneuron clusters in the three-dimensional space of the mouse visual cortex. (2014)
  • Author(s): 蝦名鉄平、惣谷和広、今吉格、Yin Shu-Ting、木村塁、柳川右千夫、亀田浩司、日置寛之、金子武嗣、津本 忠治
  • Organizer: 第37回日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Topological projections of direct and indirect pathway neurons in the neostriatum to the GPe. (2014)
  • Author(s): 岡本慎一郎、日置寛之、孫在隣、藤山文乃、金子武嗣
  • Organizer: 第37回日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Excitatory and inhibitory inputs to vasoactive intestinal polypeptide-expressing neurons in the mouse primary somatosensory cortex. (2014)
  • Author(s): 孫在隣、日置寛之、岡本慎一郎、金子武嗣
  • Organizer: 第37回日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Three Types of Thalamocortical Projections from the Rat Lateral Posterior Thalamic Nucleus: A Single Neuron-Tracing Study Using Viral Vectors. (2014)
  • Author(s): 中村悠、日置寛之、古田貴寛、金子武嗣
  • Organizer: 第37回日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Preferential inputs of cholecystokinin-positive neurons to the somatic compartment of parvalbumin-expressing neurons in the mouse primary somatosensory cortex. (2014)
  • Author(s): 日置寛之、孫在隣、岡本慎一郎、亀田浩司、金子武嗣
  • Organizer: 第37回日本神経科学学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Three Types of Thalamocortical Projections from the Rat Lateral Posterior Thalamic Nucleus: A Single Neuron-Tracing Study Using Viral Vectors. (2014)
  • Author(s): 中村悠、日置寛之、古田貴寛、金子武嗣
  • Organizer: 第119回日本解剖学会・全国学術集会
  • Place of Presentation: 下野市
• [Presentation] Excitatory and inhibitory inputs to parvalbumin-expressing interneurons in the mouse primary motor cortex. (2014)
  • Author(s): 日置寛之、孫 在隣、岡本 慎一郎、亀田浩司、倉本恵梨子、藤山文乃、金子武嗣
  • Organizer: 第119回日本解剖学会・全国学術集会
  • Place of Presentation: 下野市
• [Presentation] 中脳ドーパミン細胞の投射様式：非ドーパミン細胞との比較 (2014)
  • Author(s): 松田和郎、古田貴寛、中村公一、日置 寛之、金子武嗣
  • Organizer: 第119回日本解剖学会・全国学術集会
  • Place of Presentation: 下野市
• [Presentation] Excitatory and inhibitory inputs to vasoactive intestinal polypeptide-positive neurons in the mouse primary somatosensory cortex. (2014)
  • Author(s): 孫在隣、日置寛之、岡本慎一郎、金子武嗣
  • Organizer: 第119回日本解剖学会・全国学術集会
  • Place of Presentation: 下野市
• [Presentation] Optogenetic stimulation of preoptic neurons inhibits brown adipose tissue sympathetic nerve activity. (2013)
  • Author(s): Nakamura Y, Hioki H, Kataoka N, Kaneko T, Nakamura K.
  • Organizer: Experimental Biology
  • Place of Presentation: Boston, MA, USA.
• [Presentation] Direct projection from the dorsomedial hypothalamus to the rostral medullary raphe drives brown adipose tissue thermogenesis. (2013)
  • Author(s): Kataoka N, Hioki H, Kaneko T, Nakamura K.
  • Organizer: Experimental Biology
  • Place of Presentation: Boston, MA, USA.
• [Presentation] Local connections of excitatory neurons to parvalbumin-containing interneurons in motor-associated cortical areas of mice. (2013)
  • Author(s): 倉本恵梨子、日置寛之、金子武嗣
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] Thalamocortical projections of the lateral posterior nucleus: a single-neuron tracing study using viral vectors. (2013)
  • Author(s): 中村悠、日置寛之、古田貴寛、金子武嗣
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] Axonal arborization of midbrain non-dopaminergic neurons: single-cell study. (2013)
  • Author(s): 松田和郎、古田貴寛、倉本恵梨子、日置寛之、藤山文乃、金子武嗣
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] Projections of the adjacent direct and indirect neostriatal neurons to the external globus pallidus. (2013)
  • Author(s): 岡本慎一郎、日置寛之、孫在隣、金子武嗣
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] Excitatory and Inhibitory Inputs to Parvalbumin-Expressing Interneurons in the Mouse Primary Motor Cortex. (2013)
  • Author(s): 日置寛之、孫在隣、倉本恵梨子、王濤、亀田浩司、藤山文乃、金子武嗣
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] Preprodynorphin-producing interneurons constitute a subpopulation of somatostatin-positive neurons in the mouse primary somatosensory cortex. (2013)
  • Author(s): 孫在隣、日置寛之、岡本慎一郎、金子武嗣
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] Cell type-specific inhibitory inputs to dendritic and somatic compartments of parvalbumin-expressing neocortical interneuron. (2013)
  • Author(s): Hioki H, Sohn J, Okamoto S, Kameda H, Kuramoto E, Fujiyama F, Kaneko T.
  • Organizer: The 6th International Neural Microcircuit Conference
  • Place of Presentation: 岡崎
• [Presentation] Preprodynorphin-expressing interneurons constitute a subpopulation of somatostatin-positive neurons in the mouse primary somatosensory cortex. (2013)
  • Author(s): Sohn J, Hioki H, Okamoto S, Kaneko T.
  • Organizer: The 6th International Neural Microcircuit Conference
  • Place of Presentation: 岡崎
• [Presentation] 皮質抑制性神経細胞が備える特異的シナプス結合則の解明 (2013)
  • Author(s): 日置寛之
  • Organizer: 包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Excitatory and Inhibitory Inputs to Parvalbumin-Expressing Interneurons in the Mouse Primary Motor Cortex. (2013)
  • Author(s): 日置寛之、孫在隣、岡本慎一郎、王濤、亀田浩司、倉本恵梨子、藤山文乃、金子武嗣
  • Organizer: 包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] Imbalanced Network Excitability Drives Memory Replay. (2013)
  • Author(s): 乗本裕明、水沼未雅、江川尭寛、花岡健二郎、日置寛之、金子武嗣、山口瞬、長野哲雄、松木則夫、池谷裕二
  • Organizer: 包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] Hypothalamomedullary projection neurons that drive psychological stress-induced thermogenesis in brown adipose tissue and hyperthermia. (2013)
  • Author(s): Nakamura K, Kataoka N, Hioki H, Kaneko, T.
  • Organizer: The 43rd Society for Neuroscience Annual Meeting
  • Place of Presentation: San Diego, CA, USA.
• [Presentation] マウス大脳皮質ソマトスタチン要請良く生成細胞の一部はプレプロダイノルフィンを産生する (2013)
  • Author(s): 孫在隣、日置寛之、岡本慎一郎、金子武嗣
  • Organizer: 第89回日本解剖学会・近畿支部学術集会
  • Place of Presentation: 生駒市
• [Remarks] 高次脳形態学
  • URL: http://www.mbs.med.kyoto-u.ac.jp/
• [Remarks] 高次脳形態学
  • URL: http://www.mbs.med.kyoto-u.ac.jp/default.html