The ER/Golgi Protein FNDC3B Facilitates Climbing Fibre to Purkinje Cell Synapse Elimination in the Developing Mouse Cerebellum.

Synapse elimination during development is crucial for refining neural circuits by removing excess synapses formed around birth. In the neonatal cerebellum, Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During subsequent postnatal development, a single CF is strengthened and retained, while the other CFs are eliminated. Here, our PC-specific RNAi knockdown (KD) screening revealed that fibronectin type III domain containing 3B (FNDC3B), an endoplasmic reticulum protein, was involved in CF synapse elimination from around postnatal day 9 (P9) in mice. We showed that FNDC3B mRNA was expressed in PCs during CF synapse elimination. In PC-selective FNDC3B conditional knockout (FNDC3B-cKO) mice, CF synapse elimination from P10 was impaired, and the extension of CFs along PC dendrites was reduced at P21. However, these phenotypes were recovered by P40. In contrast, parallel fiber-mediated excitatory synaptic inputs and inhibitory synaptic inputs to PCs were not affected in FNDC3B-cKO mice. These results suggest that FNDC3B facilitates CF synapse elimination during postnatal development, highlighting a new role of FNDC3B in the developing brain.