前頭皮質の動的経路変更機構

• Project Area: Mechanisms underlying the functional shift of brain neural circuitry for behavioral adaptation
• Project/Area Number: 15H01456
• 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: National Institute for Physiological Sciences
• Principal Investigator: 川口 泰雄 生理学研究所, 基盤神経科学研究領域, 教授 (40169694)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2016: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2015: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 前頭皮質 / 錐体細胞 / サブタイプ / 発生 / スパイン / FS細胞 / パルブアルブミン / 抑制性結合

Outline of Annual Research Achievements

前頭皮質5層には他皮質領野と皮質下領域へ投射する錐体細胞がある。その主要なサブタイプは橋核等の脳幹・脊髄へ投射する錐体路細胞(pyramidal tract細胞、PT細胞)と、対側皮質へ投射する交連細胞(commissural細胞、COM細胞)である。私たちは、これら二つの並列出力は時間的に異なる情報を基底核の線条体に伝え、固有の局所結合選択性・シナプス伝達特性を使って、線条体出力に異なる影響を与えるという仮説を提案している。この並列出力系の機能理解を目指して、錐体細胞サブタイプの発生様式の違いを明らかにした上で、それを利用したサブタイプ選択的操作を考えている。そこで先ず、子宮内電気穿孔法を使って発生期の錐体細胞を標識し、サブタイプごとの発生時期を特定するとともに、蛍光標識された軸索の伸長様式を解析した。PT細胞・COM細胞の同定には、サブタイプ選択的に発現する転写因子であるCtip2とSatb2をマーカーとして用いた。その結果、５層錐体細胞はいずれも皮質板への移動中に中間帯で軸索を形成することがわかった。さらに、軸索の伸長方向は外側または内側の２者択一であること、外側伸長が内側伸長よりも先に現れることがわかった。これら初期軸索伸長パターンはマーカー発現からそれぞれ将来の錐体路投射と交連線維に対応すると考えられた。また、両者の切換えは深層細胞の産生時期に起こり、同じ５層内でもPT細胞がよりCOM細胞より早い時期に誕生のピークを迎えることがわかった。以上より、錐体細胞は初期軸索伸長方向から、先に生じる外側投射と後から生じる内側投射細胞の２グループに分類でき、それぞれPT、COM細胞に分化していくことがわかった。私たちは５層のPT細胞とCOM細胞は微小回路における役割が異なることを明らかにしてきたが、発生学的な点からもこれらは異なるグループに属することが分かった。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Institute of Neuroscience and Medicine(Germany)
• [Int'l Joint Research] South Valley University(Egypt)
• [Journal Article] Cortical divergent projections in mice originate from two sequentially generated, distinct populations of excitatory cortical neurons with different initial axonal outgrowth characteristics (2016)
  • Author(s): Hatanaka Y, Namikawa T, Yamauchi K, Kawaguchi Y
  • Journal Title: Cereb Cortex Volume: 26 Pages: 2257-2270
  • Peer Reviewed / Open Access
• [Journal Article] Selective thalamic innervation of rat frontal cortical neurons. (2016)
  • Author(s): Shigematsu N, Ueta Y, Mohamed AA, Hatada S, Fukuda T, Kubota Y, Kawaguchi, Y
  • Journal Title: Cerebral Cortex Volume: 26 Issue: 6 Pages: 2689-2701
  • DOI: 10.1093/cercor/bhv124
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons (2015)
  • Author(s): Kubota Y, Kondo S, Nomura M, Hatada S, Yamaguchi N, Mohamed AA, Karube F, Luebke J, Kawaguchi Y
  • Journal Title: eLife Volume: 4
  • DOI: 10.7554/elife.07919
  • NAID: 120005997706
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Computing reward prediction error: an integrated account of cortical timing and basal-ganglia pathways for appetitive and aversive learning (2015)
  • Author(s): Morita K, Kawaguchi Y
  • Journal Title: Eur J Neurosci Volume: 42 Issue: 4 Pages: 2003-2021
  • DOI: 10.1111/ejn.12994
  • Peer Reviewed / Open Access
• [Journal Article] Temporal structure of neuronal activity among cortical neuron subtypes during slow oscillations in anesthetized rats (2015)
  • Author(s): Ushimaru M, Kawaguchi Y
  • Journal Title: J Neurosci Volume: 35 Issue: 34 Pages: 11988-12001
  • DOI: 10.1523/jneurosci.5074-14.2015
  • Peer Reviewed / Open Access
• [Presentation] 前頭皮質における錐体細胞と抑制スタイルの多様性 (2017)
  • Author(s): 川口泰雄
  • Organizer: 第12回日本統合失調症学会
  • Invited
• [Presentation] Synapse density and estimated number on various neurons of the rat frontal cortex (2017)
  • Author(s): Kubota Y,Sekigawa A, Mohamed AA, Kondo S, Karube F, Tanaka Y, Kawaguchi Y
  • Organizer: 第94回日本生理学会大会
  • Invited
• [Presentation] Pyramidal cell diversity and inhibition styles in the frontal cortex (2016)
  • Author(s): Kawaguchi Y,Morishima M
  • Organizer: International Symposium on Adaptive Circuit Shift 2016
  • Place of Presentation: 同志社大学（京都府京都市）
  • Year and Date: 2016-03-04
  • Int'l Joint Research / Invited
• [Presentation] Plexin A2/A4-Semaphorin 6A signaling is involved in termination of migration for uppermost layer neurons in the mouse cerebral cortex (2016)
  • Author(s): Hatanaka Y,Kawasaki T,Hirata T,Kawaguchi Y
  • Organizer: International Symposium on Adaptive Circuit Shift 2016
  • Place of Presentation: 同志社大学（京都府京都市）
  • Year and Date: 2016-03-03
  • Int'l Joint Research
• [Presentation] Synapses from fast-spiking GABAergic neurons are tuned to specific postsynaptic target domains (2016)
  • Author(s): Kawaguchi Y,Kubota Y
  • Organizer: 新学術領域「大脳新皮質構築」終了公開国際シンポジウム
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2016-02-12
  • Int'l Joint Research / Invited
• [Presentation] PlexinA2/A4 signaling is necessary for proper termination of migration for uppermost part of layers 2/3 neurons in the mouse cerebral cortex (2016)
  • Author(s): Hatanaka Y,Kawasaki T,Hirata T,Kawaguchi Y
  • Organizer: 新学術領域「大脳新皮質構築」終了公開国際シンポジウム
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2016-02-12
  • Int'l Joint Research
• [Presentation] An excitatory and inhibitory synapse density on various neurons in the rat frontal cortex (2016)
  • Author(s): Kubota Y,Sekigawa A,Mohamed AA,Kondo S,Karube F,Tanaka Y,Kawaguchi Y
  • Organizer: EMBO Dendrites 2016 meeting
  • Int'l Joint Research
• [Presentation] GABAergic inputs to spine of striatal medium spiny neuron (2016)
  • Author(s): Kubota Y,Kawaguchi Y
  • Organizer: 第39回日本神経科学大会
• [Presentation] Proper termination of migration for uppermost part of layers 2/3 neurons requires PlexinA2/A4-Semaphorin6A signaling in the mouse cerebral cortex (2016)
  • Author(s): Hatanaka Y,Kawasaki T,Kawaguchi Y,Hirata T
  • Organizer: 第39回日本神経科学大会
• [Presentation] Corticocortical cell diversity in superficial layers of the rat frontal cortex (2016)
  • Author(s): Ueta Y,Hirai Y, Kawaguchi Y
  • Organizer: 第39回日本神経科学大会
• [Presentation] Distinct thalamocortical inputs mediate learning and execution of self-initiated movement (2016)
  • Author(s): Tanaka YH, Tanaka YR,Hira R,KondoM,Terada S,Kawaguchi Y,Matsuzaki M
  • Organizer: 第39回日本神経科学大会
• [Presentation] Activity of dopamine D2 receptor-expressing striatal neurons during decision-making task (2016)
  • Author(s): Nonomura S,Yamanaka K,Nishizawa K,Kobayashi K, Sakai Y,Kawaguchi Y,Nambu A,Isomura Y,Kimura M
  • Organizer: 第39回日本神経科学大会
• [Presentation] Interaction between GABAergic cells and two types of target-specific pyramidal cells in layer 5 of the rat frontal cortex (2016)
  • Author(s): Morishima M, Kawaguchi Y
  • Organizer: 第39回日本神経科学大会
• [Presentation] GABAergic/non-GABAergic synaptic inputs to striatal medium spiny neurons (2016)
  • Author(s): Kubota Y, Kawaguchi Y
  • Organizer: 46th annual meeting of the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Layer 5 GABAergic Circuits in the Frontal Cortex (2016)
  • Author(s): Kawaguchi Y
  • Organizer: The 7th International Neural Microcircuit Conference- Recent advances in the analysis of cortical microcircuits -
  • Int'l Joint Research / Invited
• [Presentation] Oscillatory Activities in the Cortical Networks (2016)
  • Author(s): Otsuka T, Kawaguchi Y
  • Organizer: The 7th International Neural Microcircuit Conference- Recent advances in the analysis of cortical microcircuits -
  • Int'l Joint Research
• [Presentation] Interaction between GABAergic cells and two types of target-specific pyramidal cells in layer 5 of the rat frontal cortex (2016)
  • Author(s): Morishima M, Kawaguchi Y
  • Organizer: The 7th International Neural Microcircuit Conference- Recent advances in the analysis of cortical microcircuits -
  • Int'l Joint Research
• [Presentation] Conserved dimensions of dendritic trees in cortical pyramidal cell (2016)
  • Author(s): Mohamed AA, Yamaguchi N, Hatada S,Luebke J, Kawaguchi Y, Kubota Y
  • Organizer: The 7th International Neural Microcircuit Conference- Recent advances in the analysis of cortical microcircuits -
  • Int'l Joint Research
• [Presentation] 大脳皮質パルブアルブミン細胞の歴史と謎 (2015)
  • Author(s): 川口泰雄
  • Organizer: 生理研研究会「行動システム脳科学の新展開」
  • Place of Presentation: 生理学研究所（愛知県岡崎市）
  • Year and Date: 2015-12-04
• [Presentation] An excitatory and inhibitory synapse density on various nonpyramidal cells in the rat cerebral cortex (2015)
  • Author(s): Kubota Y,Sekigawa A,Hatada S,Kawaguchi Y
  • Organizer: The 2nd East-Asia Microscopy Conference
  • Place of Presentation: The Himeji Chamber of Commerce and Industry（Himeji, Hyogo）
  • Year and Date: 2015-11-25
  • Int'l Joint Research / Invited
• [Presentation] Temporal organization of pyramidal neuron output to the striatum (2015)
  • Author(s): Kawaguchi Y
  • Organizer: International Symposium on Prediction and Decision Making 2015
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2015-10-31
  • Int'l Joint Research
• [Presentation] Functional effects of distinct innervation styles of pyramidal cells by fast spiking cortical interneurons (2015)
  • Author(s): Kubota Y,Kondo S,Nomura M,Hatada S,Yamaguchi N,Mohamed AA,Karube F,Luebke J,Kawaguchi Y
  • Organizer: 45th annual meeting of the Society for Neuroscience
  • Place of Presentation: McCormick Place （Chicago, USA）
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] Multi-compartmental models of corticopontine- and crossed corticostriatal neurons of rat frontal cortex (2015)
  • Author(s): Kondo M,Morishima M,Kawaguchi Y,Morita K
  • Organizer: 11th Bernstein Conference 2015
  • Place of Presentation: Neue Universitaet (Heidelberg, Germany)
  • Year and Date: 2015-09-15
  • Int'l Joint Research
• [Presentation] Correlative light and electron microscopy of brain tissue using two-photon microscope and FIB/SEM (2015)
  • Author(s): Kubota Y,Villa KL,Berry KP,Subramanian J,Cha JW,So PT,Nedivi E,Kawaguchi Y
  • Organizer: Microscopy & Microanalysis 2015
  • Place of Presentation: Oregon Convention Center (Portland, USA)
  • Year and Date: 2015-08-03
  • Int'l Joint Research
• [Presentation] 徐波振動における前頭皮質ニューロンの発火時系列 (2015)
  • Author(s): 牛丸弥香、川口泰雄
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-30
• [Presentation] Interaction between two types of pyramidal cells and GABAergic cells in the layer 5 of the frontal cortex (2015)
  • Author(s): 森島美絵子、川口泰雄
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-30
• [Presentation] Conserved morphology of dendritic trees in cortical pyramidal cell (2015)
  • Author(s): Mohamed AA,Kubota Y,Kondo S,Yamaguchi N,Hatada S,Nomura M,Younes HA,Tanaka YR,Abdalla KEH,Luebke J,Kawaguchi Y
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-29
• [Remarks] 生理学研究所大脳神経回路論研究部門
  • URL: http://www.nips.ac.jp/circuit/