抄録
Parallel fibers (PFs), axons of cerebellar granule cells, transmit multimodal sensory information via mossy fiber inputs originating from the pontine nuclei. Each PF forms synapses with multiple Purkinje cells (PCs) whose plasticity is believed to play cardinal roles in motor learning. In addition, PF-PC synapses were reported to be dynamically reorganized in an activity-dependent manner even in adulthood. Several lines of evidence have suggested that the δ2 glutamate receptor (GluRδ2) is one of the key molecules that regulate functions of PF-PC synapses; GluRδ2-null mice show ataxia and loss of long-term depression (LTD), a putative cellular model of cerebellar information storage. In addition, GluRδ2-null mice display half the number of PF-PC synapses. Despite their importance, the mechanisms by which GluRδ2 participates in PF-PC synaptic functions have been elusive, mainly because it is not activated by glutamate analogs. To gain insight into GluRδ2's mechanisms, we developed a Sindbis virus vector that express a wild-type GluRδ2. By introducing this virus vector into GluRδ2-null cerebellum in vivo, we could rescue several abnormal phenotypes, such as impaired LTD and enhanced paired-pulse facilitation of excitatory postsynaptic currents at PF-PCs synapses. This virus-based method has several advantages over non-viral conventional gene expression methods and transgenic techniques. Based on studies expressing a mutant GluRδ2, in which several functional domains were mutated, GluRδ2's mechanisms in controlling PF-PC synapses will be discussed. [J Physiol Sci. 2006;56 Suppl:S60]
