Analysis on the cerebellar neuronal circuitry that is related to autism spectrum disorders based on molecular expression patterns

• Project/Area Number: 26430035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Fujita Hirofumi 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (60725901)
• Co-Investigator(Kenkyū-buntansha): 杉原 泉 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (60187656)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小脳 / 自閉症スペクトラム障害 / マウス / マーモセット / Pcdh10 / 比較解剖 / 神経発生 / 神経回路 / 形成過程 / プルキンエ細胞 / 小葉

Outline of Final Research Achievements

Cerebellar lobules VI-VII are closely related to autism spectrum disorder syndrome (ASD). We analyzed structure, development and axonal projection patterns of these lobules in primates and rodents. Crus I and crus II lobules, which are the hemispheric part of lobules VI-VII, are well-developed in the primate cerebellum. We demonstrated that a combination of both of crus I and crus II in the primate is homologous only to the lobule that is defined as crus I in the rodent. Crus I of the rodent cerebellum contained large Pcdh10-positive compartments and had specific axonal projection patterns. Furthermore, transverse growth of Pcdh10-positive compartments occurred specifically in the developing lobules VI-VII and crus I. These results support the uniqueness of structure and input-output axonal projections of lobules VI-VII and crus I of the mammalian cerebellum.

Research Products

• [Int'l Joint Research] ジョンズ・ホプキンス大学(米国)
• [Journal Article] Lobular homology in cerebellum hemispheres of humans, non-human primates and rodents: a structural, axonal tracing and molecular expression analysis. (2017)
  • Author(s): Luo Y, Fujita H, Nedelescu H, Biswas MS, Sato C, Ying S, Takahashi M, Akita K, Higashi T, Aoki I, Sugihara I.
  • Journal Title: Brain Structure and Function Volume: 印刷中 Issue: 6 Pages: 2449-2472
  • DOI: 10.1007/s00429-017-1436-9
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Spatial rearrangement of Purkinje cell subsets forms the transverse and longitudinal compartmentalization in the mouse embryonic cerebellum. (2017)
  • Author(s): Vibulyaseck S, Fujita H, Luo Y, Anh KT, Oh-Nishi A, Ono Y, Hirano S, Sugihara, I.
  • Journal Title: Journal of Comparative Neurology Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Compartmentalization of the chick cerebellar cortex based on the link between the striped expression pattern of aldolase C and the topographic olivocerebellar projection (2015)
  • Author(s): Vibulyaseck S, Luo Y, Fujita H, Oh-Nishi A, Ohki-Hamazaki H, Sugihara
  • Journal Title: J Comp Neurol Volume: 印刷中 Issue: 13 Pages: 1886-1912
  • DOI: 10.1002/cne.23769
  • Peer Reviewed
• [Journal Article] Detailed expression pattern of aldolase C (aldoc) in the cerebellum, retina and other areas of the CNS studied in aldoc-venus knock-in mice. (2014)
  • Author(s): Fujita H, Aoki H, Ajioka I, Yamazaki M, Abe M, Oh-Nishi A, Sakimura K, Sugihara I.
  • Journal Title: PLoS One. Volume: 9(1) Issue: 1 Pages: e86679-e86679
  • DOI: 10.1371/journal.pone.0086679
  • Peer Reviewed / Open Access
• [Journal Article] Systematic analysis of neuronal wiring of the rodent deep cerebellar nuclei reveals differences reflecting adaptations at the neuronal circuit and internuclear level (2014)
  • Author(s): Hamodeh S, Baizer J, Sugihara I, Sultan F
  • Journal Title: J Comp Neurol Volume: 522(11) Issue: 11 Pages: 2481-2497
  • DOI: 10.1002/cne.23545
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cerebellar afferents originating from the medullary reticular formation that are different from mossy, climbing or monoaminergic fibers in the rat (2014)
  • Author(s): Luo Y, Sugihara I
  • Journal Title: Brain Res Volume: 1566 Pages: 31-46
  • DOI: 10.1016/j.brainres.2014.04.020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Systematic regional variations in Purkinje cell spiking patterns. (2014)
  • Author(s): Xiao J, Cerminara NL, Kotsurovskyy Y, Aoki H, Burroughs A, Wise AK, Luo Y, Marshall SP, Sugihara I, Apps R, Lang EJ
  • Journal Title: PLoS ONE Volume: 9 Issue: 8 Pages: e105633-e105633
  • DOI: 10.1371/journal.pone.0105633
  • Peer Reviewed / Open Access
• [Journal Article] Modulation of Purkinje cell complex spike waveform by synchrony levels in the olivocerebellar system. (2014)
  • Author(s): Lang EJ, Tang T, Suh CY, Xiao J, Kotsurovskyy Y, Blenkinsop TA, Marshall SP, Sugihara I
  • Journal Title: Front Syst Neurosci Volume: 8 Pages: 210-210
  • DOI: 10.3389/fnsys.2014.00210
  • Peer Reviewed / Open Access
• [Presentation] Early development of the longitudinal striped compartments in the prenatal mouse cerebellum studied with three-dimensional mapping of Protocadherin 10 expression (2016)
  • Author(s): Vibulyaseck S, Sarpong GA, Fujita H, Hirano S, Sugihara I.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-07-20
• [Presentation] マカク、マーモセット、ラット、マウスにおける、ヒト小脳の第I/II脚と相同の小脳小葉の同定 (2016)
  • Author(s): Luo Y, Fujita H, Hermina N, Sato C, Ying S, Takahashi M, Biswas MS, Akita K, Aoki I, Sugihara I
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-07-20
• [Presentation] 小葉の立体構造、軸索投射、分子発現パタンの解析に基づくヒト、ニホンザル、マーモセット、ラット、マウスの小脳半球部小葉構造の相同性 (2016)
  • Author(s): 杉原泉
  • Organizer: 第121回日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま、福島県郡山市
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Morphologically, molecularly, and functionally distinct classes of neurons in the medial cerebellar output nucleus. (2016)
  • Author(s): Hirofumi Fujita, Takashi Kodama, Sascha du Lac
  • Organizer: 第121回日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま、福島県郡山市
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] アルドラーゼC発現の縞構造と登上線維投射の部位対応性に基づいたトリ小脳の区画構造 (2014)
  • Author(s): Yuanjun Luo, Suteera Vibulyaseck, Hirofumi Fujita, Hiroko Ohki-Hamazaki, and Izumi Sugihara
  • Organizer: 平成26年度『包括型脳科学研究推進支援ネットワーク』冬のシンポジウム
  • Place of Presentation: 東京医科歯科大学･ホテル東京ガーデンパレス、東京都文京区
  • Year and Date: 2014-12-11 – 2014-12-13
• [Book] Essentials of Cerebellum and Cerebellar Disorders. A Primer For Graduate Students. (2016)
  • Author(s): Luo Y, Sugihara I
  • Total Pages: 7
  • Publisher: Springer
• [Remarks] 東京医科歯科大学大学院医歯学総合研究科 システム神経生理学分野
  • URL: http://www.tmd.ac.jp/med/phy1/phy1.html