The transcription factor ZFP64 promotes activity-dependent synapse elimination during postnatal cerebellar development

Eliminating redundant synapses formed around birth is essential for shaping functionally mature neural circuits during postnatal development. Each Purkinje cell (PC) in the neonatal mouse cerebellum receives synaptic inputs from multiple climbing fibers (CFs). Only one CF is strengthened and extends its innervation over PC dendrites, whereas the other CFs are eventually pruned during postnatal development. These events are believed to require proper gene expression, but the underlying mechanisms are not yet understood. Here, we report that the transcription factor ZFP64 in PCs mediates part of CF synapse elimination events presumably downstream of P/Q-type voltage-dependent Ca²⁺ channels (P/Q-VDCCs). PC-specific knockdown (KD) of ZFP64 during postnatal development delayed the elimination of redundant CF synapses and the dendritic extension of CF innervation. The KD of semaphorin 3A (Sema3A) in PCs partially restored the effects of ZFP64 or P/Q-VDCC KD. We propose that ZFP64 promotes developmental CF synapse elimination by regulating Sema3A expression.