title: Arc/Arg3.1 is a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum.
abstract: Neural 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 Ca(2+) 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.
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Mikuni
authors.forename: Naofumi
authors.initials: N
authors.lastname: Uesaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okuno
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055366:Synaptic Potentials / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein