2017 Fiscal Year Final Research Report
Elucidation of the link of gene, neural circuit, and behavior in the mouse olfactory system
| 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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| 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 |
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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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| Free Research Field |
分子生物学
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