Abstract
The δ2 glutamate receptor (δ2 receptor) is predominantly expressed at parallel fiber (PF)-Purkinje cell (PC) synapses. Knock-out of the δ2 receptor gene causes abnormal phenotype such as loss of LTD induction, impaired synaptogenesis between PF and PCs and persistent innervations of PCs by multiple climbing fibers, resulting in severe ataxia. The δ2 receptor is classified in ionotropic glutamate receptors; however, it has been elusive whether the δ2 receptor is activated by glutamate or related amino acids and working as a cation-permeable ion channel. We produced a δ2 receptor deletion construct that lacks conserved glutamate binding domains (S1 and S2) and ion-channel-pore-forming transmembrane domains (TM1–TM3). The construct (NTD-TM4-CTD) consists of the extracellular N-terminal domain (NTD), TM4 and intracellular C-terminal domain (CTD). Using lentiviral vectors, the NTD-TM4-CTD was expressed in P6 PCs of δ2 receptor-deficient mice, and the mice were analyzed at P25–P35. Surprisingly, the rotarod performance was significantly superior in infected mice to their non-infected littermates. Patch-clamp analysis showed that innervation of δ2-receptor-null PCs by multiple climbing fibers was significantly rescued by NTD-TM4-CTD expression. These results indicate that the δ2 receptor is neither a glutamate receptor nor an ion channel, but a membrane protein that is associated with cerebellar synapse formation presumably by interacting the extracellular NTD with an unidentified ligand. [J Physiol Sci. 2008;58 Suppl:S125]
