Arc/Arg3.1 Is a Postsynaptic Mediator of Activity-Dependent Synapse Elimination in the Developing Cerebellum

• Optogenetic elevation of Purkinje cell (PC) activity accelerates synapse elimination
• The acceleration requires Ca2+ elevation and Arc induction in PCs
• Arc mediates synapse elimination downstream of P/Q-type Ca2+ channels in PCs
• Arc is essential for removal of redundant synapses from PC somata

SummaryNeural circuits are shaped by activity-dependent elimination of redundant synapses during postnatal development. In many systems, postsynaptic activity is known to be crucial, but the precise mechanisms remain elusive. Here, we report that the immediate early gene Arc/Arg3.1 mediates elimination of surplus climbing fiber (CF) to Purkinje cell (PC) synapses in the developing cerebellum. CF synapse elimination was accelerated when activity of channelrhodopsin-2-expressing PCs was elevated by 2-day photostimulation. This acceleration was suppressed by PC-specific knockdown of either the P/Q-type voltage-dependent Ca2+ channels (VDCCs) or Arc. PC-specific Arc knockdown had no appreciable effect until around postnatal day 11 but significantly impaired CF synapse elimination thereafter, leaving redundant CF terminals on PC somata. The effect of Arc knockdown was occluded by simultaneous knockdown of P/Q-type VDCCs in PCs. We conclude that Arc mediates the final stage of CF synapse elimination downstream of P/Q-type VDCCs by removing CF synapses from PC somata.