選ばれた接続を強く育てる脳の仕組みを解明～小脳神経回路形成におけるmGluR1シグナルの意外な二役～

2026-01-29 北海道大学,帝京大学,東京大学,広島大学

本研究で解明されたmGluR1シグナルの役割。本研究により、mGluR1-PKCγ経路は、選ばれた「勝者」線維のシナプス構造・機能の強化と、それに続く樹状突起への支配領域の拡大に必須であることが明らかになった。これまでに知られていた「敗者」の除去(シナプス刈り込み)に加え、選ばれた接続を強く育てるという「育成」の役割も併せ持つ。

<関連情報>

• https://www.hokudai.ac.jp/news/2026/01/mglur1.html
• https://www.hokudai.ac.jp/news/pdf/260129_pr.pdf
• https://www.pnas.org/doi/10.1073/pnas.2425460123

mGluR1シグナル伝達経路は「勝者」登上線維シナプスの強化に必須である mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum

Miwako Yamasaki, Taisuke Miyazaki, Kouichi Hashimoto, +3 , and Masahiko Watanabe
Proceeding of the National Academy of Science  Published:January 23, 2026
DOI:https://doi.org/10.1073/pnas.2425460123

Significance

The precise formation of neural circuits relies on both the selective strengthening of frequently used synaptic inputs and the elimination of redundant connections. In cerebellar Purkinje cells, strengthening a single “winner” climbing fiber (CF) is key to establishing efficient synaptic wiring. Although signaling via metabotropic glutamate receptor 1 (mGluR1) and protein kinase Cγ (PKCγ) mediates elimination of “loser” CFs, its role in maturing the “winner” CF has remained unclear. This study shows that this pathway is crucial for homosynaptic long-term potentiation, selective postsynaptic strengthening, and expansion of the dendritic innervation territory of the “winner” CF. These findings uncover a dual role for mGluR1–PKCγ signaling in eliminating “loser” CF inputs and maturing “winner” CF synapses, thereby shaping precise cerebellar circuits.

Abstract

Functional neural circuits are sculpted by strengthening frequently used synapses and removing unnecessary connections. At birth, cerebellar Purkinje cells receive inputs with similar synaptic strengths from multiple climbing fibers (CFs). During postnatal development, a single “winner” CF is selectively strengthened and expands its dendritic innervation territory, while somatic “loser” synapses are eliminated. Here, we report that deleting metabotropic glutamate receptor 1 (mGluR1) or protein kinase Cγ (PKCγ) in mice disrupts this selective strengthening and territory expansion of “winner” CFs during early development. This impairment leads to weaker synaptic transmission and diminished dendritic innervation territory of “winner” CFs at later stages. Notably, “winner” CF synapses in these mutants exhibit impaired long-term potentiation, reduced AMPA receptor expression, and simpler postsynaptic organizations. These findings reveal a previously unappreciated role for mGluR1–PKCγ signaling, besides its established role in eliminating “loser” CFs, in promoting the functional and structural maturation of “winner” CF synapses.