The extreme C-terminus of GluRδ2 is essential for induction of long-term depression in cerebellar slices

Long-term depression (LTD) of parallel fibre (PF)-Purkinje cell synapses in the cerebellum is recognized as a cellular substrate of motor learning. Although the delta 2 glutamate receptor (GluR delta 2) has been shown to be crucial for LTD, the mechanisms by which GluR delta 2 functions remain elusive. In this study, we developed a virus vector-based gene transfer approach to rescue impaired LTD in GluR delta 2-null Purkinje cells in cerebellar slice preparations. We demonstrated that LTD was restored in GluR delta 2-null Purkinje cells transduced with wild-type but not with mutant GluR delta 2, which lacked the PDZ-ligand domain in the C-terminus. Immunohistochemical analysis revealed no difference in expression levels or spine localization patterns between virally introduced wild-type and mutant GluR delta 2 proteins. Similarly, LTD was abrogated in Purkinje cells that had been acutely perfused with peptides, hampering the interaction of GluR delta 2 with PDZ proteins such as PSD-93, PTPMEG and S-SCAM but not with delphilin. Together, these results indicate that PDZ proteins that bind to the C-terminus of GluR delta 2 are not essential for localizing GluR delta 2 at synapses but are crucial for conveying signals necessary for the induction of LTD.