Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Pur- kinje cell synapses is thought to regulate motor learning and memory formation in the cere- bellum. Neuronal activity-evoked protein kinase C (PKC) activation is required for the in- duction of LTD. In addition, theδ2 glutamate receptor (GluRδ2), which is predominantly expressed at PF-Purkinje cell synapses, is indispensable for the induction of LTD; however, the mechanisms by which GluRδ2 regulates LTD and its relationship with PKC activation remain elusive. Interestingly, GluRδ2 is phosphorylated by PKC on serine 945 (Ser945) near its C-terminus and a postsynaptic protein S-SCAM, which could potentially regulate glutamate receptor trafficking and synaptic plasticity, binds to the extreme C-terminus of GluRδ2 in a phosphorylation-dependent manner on Ser945. Here, using a Sindbis-based vi- rus expression approach, we show that a mutant GluRδ2, in which alanine replaced Ser945 and did not undergo PKC phosphorylation, was normally localized at the postsynaptic sites of PF-Purkinje cell synapses. In addition, like wild-type GluRδ2, the phosphorylation-dis- rupted GluRδ2 successfully rescued abrogated LTD in GluR δ2-null Purkinje cells. These re- sults indicate that Ser945, a major PKC phosphorylation site of of GluRδ2, may not play a crucial role in induction of LTD in the cerebellum. (Keio J Med 57 (2) : 105-110, June 2008)