Plasticity at the parallel fiber (PF)-Purkinje cell synapses is a putative cellular model of the cerebellar information storage. Predominantly expressed in Purkinje cells, the δ2 glutamate receptor (GluRδ2) plays a crucial role in regulating synaptic plasticity at the PF-Purkinje cell synapses and cerebellar functions; mutant mice deficient in GluRδ2 (GluRδ2−/−) display impaired synapse formation and long-term depression (LTD) in the cerebellum. Nevertheless, the mechanism by which GluRδ2 functions in vivo has remained elusive. Previously, by using Sindbis virus-mediated expression system, we demonstrated that the most carboxy-terminal (C-terminal) domain of GluRδ2, which interacts with several PDZ proteins, is required for LTD induction (Kohda et al., J. Physiol. Sci. 56 Suppl., S166, 2006). To further examine the importance of the PDZ binding motif of GluRδ2 in cerebellar functions in vivo, we introduced a mutant GluRδ2 transgene lacking seven amino acids of the most C-terminal domain (GluRδ2DCT7), into GluRδ2−/− mice. Although GluRδ2DCT7 proteins were expressed at PF-Purkinje cell synapses to a sufficient level required for rescuing all phenotypes of GluRδ2−/− mice, LTD was still severely impaired in these mice, consistent with our previous study using a Sindbis virus. Furthermore, the mice showed poor performance in a rotor-rod test and an eye-blink conditioning task, reflecting impaired cerebellum-dependent motor learning. Taken together, the PDZ binding motif at the C-terminus of GluRδ2 plays an indispensable role for LTD induction and motor learning in the cerebellum. [J Physiol Sci. 2007;57 Suppl:S19]
