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Professor Kano discovered that synaptic transmission is not necessary for selecting "winners" but is essential for the "refinement" of wiring.Itabashi Campus

On Tuesday, August 26, 2025, Teikyo University Advanced Comprehensive Research Organization Specially Appointed Professor Kano Yoshinobu (Honorary Professor, Graduate School of Medicine, The University of Tokyo Graduate School), Kao Tzu-Huei, Research Fellow at the Graduate School of Medicine, The University of Tokyo Graduate School (at the time of the research), Yuto Okuno, Research Fellow Advanced Comprehensive Research Organization Teikyo University, and Naofumi Uesaka, Senior Assistant Professor Graduate School Graduate School of Medicine, The University of Tokyo (currently the Graduate School of Medicine and Dentistry, Tokyo University of Science Professor at the time of the study) A research group led by Naofumi Uesaka and others has clarified how ascending fibers that synapse into Purkinje cells, which are responsible for not only motor control but also social and cognitive functions, "survive" in the early stages of development, and how they remove unnecessary fibers to complete adult neural circuits.

Immediately after birth, Purkinje cells in mice receive synaptic connections from five or more climbing fibers. It has traditionally been thought that, among these multiple climbing fibers, those that can send strong signals (synaptic transmission) to Purkinje cells survive as "winners," while those that can only send weak signals are eliminated as "losers." To test this hypothesis, this study genetically inhibited the release of a neurotransmitter (glutamate) from some climbing fibers, preventing them from sending signals to Purkinje cells, and examined how this affected the formation of neural circuits in the developing cerebellum.
The results showed that early "winner" selection can occur even without synaptic transmission. However, synaptic transmission is essential for refinement, in which selected climbing fibers expand the area where they synapse with Purkinje cell dendrites and eliminate other fibers to complete the final wiring. It was also confirmed that inhibiting synaptic transmission results in immature wiring remaining for a long period of time.
These results suggest that neural circuit formation during development proceeds in two stages: (1) a "selection" phase that does not require synaptic transmission, and (2) a "refinement" phase that depends on synaptic transmission. This provides a new perspective for understanding and exploring therapeutic targets for diseases involving subtle abnormalities in neural circuits, such as developmental disorders and ataxia. In other words, the greatest significance of this research is that it experimentally supports the existence of a "division of labor" in which nerve fibers that survive are first selected regardless of synaptic transmission, and then the wiring is refined by a mechanism that depends on synaptic transmission.

The results of this research were published in the Proceedings of the National Academy of Sciences of the United States of America at 4:00 a.m. (Japan time) on Friday, August 22, 2025.

Click here for the press release
The published paper is here
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