選ばれた神経だけが強くなる――脳の勝者総取り戦略~シナプスの構造的な強化を3次元で可視化~

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2025-04-11 北海道⼤学

北海道大学大学院医学研究院の山崎美和子准教授らの研究グループは、発達期のマウス小脳において、プルキンエ細胞と登上線維のシナプス接続が「勝者総取り」戦略により選別・強化される過程を、3次元電子顕微鏡と免疫組織化学を用いて可視化しました。研究では、「勝者」となる登上線維が、細胞体および樹状突起において広く複雑なシナプス構造を形成し、AMPA型グルタミン酸受容体や神経伝達物質放出に関与するRIM分子の発現が特異的に高いことが明らかになりました。これらの成果は、神経回路の精緻化における構造的・分子的基盤を示すものであり、2025年4月10日にThe Journal of Neuroscience誌に掲載され、表紙論文として紹介されました。

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発達期マウス小脳における登上線維―プルキンエ細胞シナプスの分子解剖学的強化 Molecular and Anatomical Strengthening of “Winner” Climbing Fiber Synapses in Developing Mouse Purkinje Cells

Asako Nitta, Miwako Yamasaki, Taisuke Miyazaki, Kohtarou Konno, Haruto Yoshimura and Masahiko Watanabe
The Journal of Neuroscience  Published:9 April 2025
DOI:https://doi.org/10.1523/JNEUROSCI.2156-24.2025

選ばれた神経だけが強くなる――脳の勝者総取り戦略~シナプスの構造的な強化を3次元で可視化~

Abstract

Neural circuits are refined by strengthening frequently used or advantaged synapses while eliminating redundant connections. In neonatal mice, cerebellar Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) of similar strength. By postnatal day 7 (P7), one CF, the “winner,” is selectively strengthened and begins dendritic translocation by P9, while both “winner” and “loser” CFs temporarily maintain somatic synapses. Although the functional differentiation of CF inputs is well understood, their structural differentiation is less clear. In this study, we examined “winner” CF synapses in dendrites and both “winner” and “loser” synapses in the soma using serial electron microscopy and immunohistochemistry in C57BL/6 mice. We found that “winner” CF synapses, both in the soma and dendrites, developed more complex pre- and postsynaptic structures than “loser” CFs, with an expanded area of postsynaptic density. Additionally, “winner” CF synapses expressed significantly higher levels of AMPA-type glutamate receptors. Notably, only dendritic “winner” synapses showed increased levels of Rab3-interacting molecule RIM, a key presynaptic regulator of neurotransmitter release. These findings reveal the molecular and structural features that enable “winner” CFs to reinforce their synaptic strength and innervation, allowing them to outcompete other inputs during early development.

生物工学一般
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