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

• 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

SummarySynapse 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.

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