Molecular mechanisms underlying subnetwork formation in V1

• Project/Area Number: 26430029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Teikyo University (2017); National Institute for Physiological Sciences (2014-2016)
• Principal Investigator: Miyashita Toshio 帝京大学, 医学部, 講師 (80415314)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 一次視覚野 / in vivo カルシウムイメージング / 微小神経回路 / 大脳皮質 / ２光子顕微鏡イメージング / Cal590 / Dnmt3b / cPcdh / カルシウムイメージング / プロトカドヘリン / 視覚応答 / 局所回路 / 二光子イメージング / 局所神経回路 / サブネットワーク / 多光子励起顕微鏡 / 大脳皮質局所神経回路

Outline of Final Research Achievements

Specific neuronal connections (subnetworks) in the sensory cortex are thought to be fundamental for information processing. Some studies have suggested a cell lineage contribution to establish cortical subnetworks. That is, excitatory neurons arising from a same neural progenitor cell have shown higher synaptic connection probabilities and responses to similar sensory stimuli.
However, little is known about the molecular mechanisms for subnetwork formation. We focused on the function of Dnmt3b, which regulates the expression of cPcdh isoforms, a family of adhesion molecules, in the neural progenitors. We recorded the visual neural responses from Dnmt3b-KO and wild-type neurons in V1 of mice using 2 Photon Ca2+ imaging. We observed: (i) the response strengths of Dnmt3b-KO neurons were comparable to normal neurons, and (ii) lower orientation tuning (OSI) in Dnmt3b-KO neurons. These results suggest the involvement of Dnmt3b in the establishment of cortical neural network specifications.

Research Products

• [Journal Article] Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins (2016)
  • Author(s): Tarusawa E., Sanbo M., Okayama A., Miyashita T., Kitsukawa T., Hirayama T., Hirabayashi T., Hasegawa S., Kaneko R., Toyoda S., Kobayashi T., Kato-Itoh M., Nakauchi H., Hirabayashi M., Yagi T., Yoshimura Y.
  • Journal Title: BMC Biology Volume: 14 Issue: 1 Pages: 103-103
  • DOI: 10.1186/s12915-016-0326-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 大脳皮質神経細胞群の多様な個性の獲得におけるDNAメチル化の関与 (2018)
  • Author(s): 宮下俊雄、 三宝誠，平林真澄，八木健，吉村由美子
  • Organizer: 第123回日本解剖学会総会・全国学術集会
• [Presentation] High reciprocal connectivity between clonal cortical neurons is established under the guidance of epigenetic regulation. (2016)
  • Author(s): 9.Tarusawa E, Sanbo M, Okayama A, Miyashita T, Kitsukawa T, Hirayama T, Hirabayashi T, Hasegawa S, Hirabayashi M, Yagi T, Yoshimura Y.
  • Organizer: Society of Neuroscience 2016
  • Place of Presentation: san diego convention center, CA, USA
  • Year and Date: 2016-11-16
  • Int'l Joint Research