Regulation of long-term depression and climbing fiber territory by glutamate receptor δ2 at parallel fiber synapses through its c-terminal domain in cerebellar Purkinje cells

Glutamate receptor ( GluR) delta 2 selectively expressed in cerebellar Purkinje cells ( PCs) plays key roles in long-term depression ( LTD) induction at parallel fiber ( PF)-PC synapses, motor learning, the matching and connection of PF-PC synapses in developing and adult cerebella, the elimination of multiple climbing fibers ( CFs) during development, and the regulation of CF territory on PCs. However, it remains unsolved how GluR delta 2 regulates cerebellar synaptic plasticity, PF-PC synapse formation, and CF wiring. One possible signaling mechanism through GluR delta 2 is signaling by protein-protein interactions. The C-terminal region of GluR delta 2 contains at least three domains for protein-protein interactions. The PDZ ( postsynaptic density-95/Discs large/zona occludens 1)-binding domain at the C terminal, named as the T site, interacts with several postsynaptic density proteins. Here, we generated GluR delta 2 Delta T mice carrying mutant GluR delta 2 lacking the T site. There were no significant differences in the amount of receptor proteins at synapses, histological features, and the fine structures of PF-PC synapses between wild-type and GluR delta 2 Delta T mice. However, LTD induction at PF-PC synapses and improvement in the accelerating rotarod test were impaired in GluR delta 2 Delta T mice. Furthermore, CF territory expanded distally and ectopic innervation of CFs occurred at distal dendrites in GluR delta 2 Delta T mice, but the elimination of surplus CF innervation at proximal dendrites appeared to proceed normally. These results suggest that the C-terminal T site of GluR delta 2 is essential for LTD induction and the regulation of CF territory but is dispensable for PF-PC synapse formation and the elimination of surplus CFs at proximal dendrites during development.