Contribution of postsynaptic GluD2 to presynaptic R-type Ca(2+) channel function, glutamate release and long-term...

Glutamate-receptor-like molecule delta2 (GluD2) is selectively expressed on the postsynaptic membranes at parallel fiber to Purkinje cell (PF-PC) synapses in the cerebellum. GluD2 plays critical roles not only in postsynaptic long-term depression but also in the induction of presynaptic differentiation through trans-synaptic interaction with neurexin. However, how GluD2 influences the presynaptic function remains unknown. Here, effects of the deletion of postsynaptic GluD2 on the presynaptic properties were studied focusing on the paired pulse ratio (PPR) of two consecutive EPSC amplitudes, which was larger in GluD2 knockout mice. The PPR difference remained even if saturation of glutamate binding to postsynaptic receptors was suppressed, confirming the presynaptic difference between the genotypes. We then explored the possibility that presynaptic voltage-gated Ca(2+) channels (VGCCs) are affected in GluD2 knockout mice. Application of selective blockers for specific VGCCs indicated that R-type but not P/Q- or N-type VGCC, was affected in the mutant mice. Furthermore, presynaptic long-term potentiation (LTP) at PF-PC synapses, which requires R-type VGCC, was impaired in GluD2 knockout mice. These results suggest that GluD2 deletion impairs presynaptic R-type VGCC, resulting in decreased release of synaptic vesicles, and also in the impairment of presynaptic LTP at PF-PC synapses.