Synaptic transmission is dispensable for selecting the winner input but is crucial for the subsequent events of synapse elimination

• 成果类型: Article
• 署名作者: Kao, Tzu- Huei; Okuno, Yuto; Matsuyama, Kyoko; Watanabe, Takaki; Uesaka, Naofumi; Kano, Masanobu
• 署名单位: University of Tokyo; University of Tokyo; Teikyo University; Institute of Science Tokyo
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14499
• DOI: 10.1073/pnas.2416797122
• 发表日期: 2025-08-26
• 关键词: cerebellar purkinje-cells; climbing fiber synapse; mice lacking; innervation; refinement; parallel; mglur1; translocation; COMPETITION; regression

摘要

Synaptic transmission has long been thought to regulate neuronal wiring during postnatal development, but this assumption remains largely untested. Selective strengthening of a single winner climbing fiber (CF) afferent to each Purkinje cell (PC) and elimination of the other loser CF axons in the cerebellum has been a representative model of neural circuit refinement. Here, we examined the role of neurotransmission at CF-PC synapses in their postnatal development. We labeled a subset of CFs in neonatal mice with fluorescent markers and the tetanus toxin light chain to ablate neurotransmitter release from these CFs. Surprisingly, we found that such neurotransmitter release-deficient CFs were able to become the winners. However, synaptic transmission was crucial for the winning CF to extend its synaptic territory along the PC dendritic arbor and eliminate the loser CFs. These findings reveal how synaptic transmission governs multiple steps of synapse elimination but not the selection of the winner input that persists throughout life.