Global Scaling Down of Excitatory Postsynaptic Responses in Cerebellar Purkinje Cells Impairs Developmental Synapse Elimination

Synapse elimination is crucial for precise neural circuit formation during postnatal development. We examined how relative differences in synaptic strengths among competing inputs and/or absolute synaptic strengths contribute to climbing fiber (CF) to Purkinje cell (PC) synapse elimination in the cerebellum. We generated mice with PC-selective deletion of stargazin (TARP γ-2), the major AMPA receptor auxiliary subunit in PCs (γ-2 PC-KO mice). Whereas relative differences between “strong” and “weak” CF-mediated postsynaptic response are preserved, absolute strengths of CF inputs are scaled down globally in PCs of γ-2 PC-KO mice. Although the early phase of CF elimination is normal, dendritic translocation of the strongest CF and the late phase of CF elimination that requires Ca2+-dependent activation of Arc/Arg3.1 in PCs are both impaired in γ-2 PC-KO mice. We conclude that, although relative differences in CF synaptic inputs are initially essential, proper synaptic scaling is crucial for accomplishing CF synapse elimination. [Display omitted] •Deletion of TARPγ-2 in Purkinje cells globally scales down their excitatory responses•The γ-2 deletion impairs translocation of the strongest climbing fibers to dendrites•The scaling down impairs the late phase of climbing fiber synapse elimination•Insufficient activation of Arc is a major cause of impaired synapse elimination Kawata et al. examined how global scaling down of excitatory postsynaptic responses in mouse cerebellar Purkinje cells (PCs) affects developmental elimination of redundant climbing fiber (CF) synapses. Scaling down did not affect the early phase of CF elimination, but impaired the translocation of the strongest CF to PC dendrites and the late phase of CF elimination that requires Ca2+-dependent activation of Arc in PCs. The results indicate that proper synaptic scaling is crucial for accomplishing developmental synapse elimination.