| Project/Area Number |
24000014
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Fukui (2013-2017)
The University of Tokyo (2012) |
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Principal Investigator |
Sakano Hitoshi 福井大学, 学術研究院医学系部門, 特命教授 (90262154)
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| Co-Investigator(Kenkyū-buntansha) |
Nureki Osamu 東京大学, 大学院理学系研究科, 教授 (10272460)
Nishizumi Hirofumi 東京大学, 大学院理学系研究科, 助教 (30292832)
Kikusui Takefumi 麻布大学, 獣医学部, 教授 (90302596)
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| Research Collaborator |
Tsubokawa Tokiko 福井大学, 学術研究院医学系部門, 特命職員
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| Project Period (FY) |
2012 – 2017
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥457,600,000 (Direct Cost: ¥352,000,000、Indirect Cost: ¥105,600,000)
Fiscal Year 2016: ¥90,350,000 (Direct Cost: ¥69,500,000、Indirect Cost: ¥20,850,000)
Fiscal Year 2015: ¥87,750,000 (Direct Cost: ¥67,500,000、Indirect Cost: ¥20,250,000)
Fiscal Year 2014: ¥91,000,000 (Direct Cost: ¥70,000,000、Indirect Cost: ¥21,000,000)
Fiscal Year 2013: ¥85,800,000 (Direct Cost: ¥66,000,000、Indirect Cost: ¥19,800,000)
Fiscal Year 2012: ¥102,700,000 (Direct Cost: ¥79,000,000、Indirect Cost: ¥23,700,000)
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| Keywords | 遺伝子操作マウス / 光遺伝学 / 恐怖反応 / 社会行動 / セマフォリン / 二次神経 / 扁桃体 / シナプス形成 / 嗅覚神経回路 / 軸索投射 / 出力判断 / 臨界期 / 刷り込み記憶 / 主嗅覚系 / 恐怖行動 / チャネルロドプシン / critical period / 行動障害 / 本能回路 / 学習回路 / 情動・行動判断 / 嗅皮質 / レヴィウイルス / 遺伝子改変マウス / 嗅球 / 狂犬病ウイルス / 二光子レーザー顕微鏡 / Neuropilin2 / Semaphorin3F / 神経回路 / 嗅覚情報処理 / 神経地図 / 嗅覚受容体 |
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| Outline of Final Research Achievements |
In mammals, neural circuits are formed based on a genetic program and refined by neuronal activity after birth. In the primary projection, expressed odorant-receptor (OR) molecules play an instructive role in guiding axons to the olfactory bulb (OB). We found that agonist-independent OR activity regulates targeting of olfactory sensory neurons (Cell, 154, 1314, 2013).
In the secondary projection, Neuropilin 2-positive (Nrp2^+) mitral cells were found to play crucial roles in transmitting attractive social signals. In the Nrp2 knockout, odor-induced social responses were perturbed. In utero electroporation demonstrated that activation of the Nrp2 is sufficient to instruct circuit formation to the anterior medial amygdala (MeA) (Nat. Commun., 8, 15977, 2017).
We also found that olfactory circuits are newly connected to second-order neurons in an activity-dependent manner. Sema7A is key for inducing post-synaptic events within glomeruli (Nat. Commun., 9, 1842, 2018). Exposure of the newborn to a particular odorant enhanced Sema7A expression in the responding glomeruli establishing imprinted memory (Nat. Neurosci., in revision).
Fox odor trimethyl thiazoline (TMT) is known to activate multiple glomeruli and elicits strong fear responses. We generated channel-rhodopsin knockin mice for one of the TMT-reactive receptors, Olfr1019, and found that photo-stimulation induced freezing/immobility responses (Nat. Commun., 8, 16011, 2017).
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| Assessment Rating |
Verification Result (Rating)
A-
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Assessment Rating |
Result (Rating)
A-: Progress in the research is steadily towards the initial goal. However, further efforts are necessary as a part of the research progress is delayed.
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