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

## TL;DR

This study shows that the protein FNDC3B helps eliminate extra synapses on Purkinje cells in the developing mouse cerebellum.

## Contribution

FNDC3B is newly identified as a facilitator of climbing fiber synapse elimination in the developing cerebellum.

## Key findings

- FNDC3B is involved in synapse elimination from postnatal day 9 in mice.
- FNDC3B deletion impairs synapse elimination and CF extension at P10 and P21, but effects are recovered by P40.
- FNDC3B does not affect parallel fiber or inhibitory synaptic inputs to Purkinje cells.

## Abstract

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.

We investigated the role of fibronectin type III domain containing 3B (FNDC3B) in climbing fiber (CF) to Purkinje cell (PC) synapse elimination during postnatal development of the mouse cerebellum. We performed PC‐specific deletion of FNDC3B by RNAi‐mediated knockdown or PC‐specific conditional knockout in mice and examined CF to PC synapse development both electrophysiologically and morphologically. Our results show that FNDC3B in PCs facilitates CF synapse elimination from around postnatal day 10 and the extension of CFs along PC dendrites, but the effects of FNDC3B deletion in PCs are recovered in the adult cerebellum.