Control of Synaptic Connection by Glutamate Receptor δ2 in the Adult Cerebellum

Abstract

Precise topological matching of presynaptic and postsynaptic specializations is essential for efficient synaptic transmission. Furthermore, synaptic connections are subjected to rearrangements throughout life. Here we examined the role of glutamate receptor (GluR) δ2 in the adult brain by inducible and cerebellar Purkinje cell (PC)-specific gene targeting under the pure C57BL/6 genetic background. Concomitant with the decrease of postsynaptic GluRδ2 proteins, presynaptic active zones shrank progressively and postsynaptic density (PSD) expanded, resulting in mismatching between presynaptic and postsynaptic specializations at parallel fiber-PC synapses. Furthermore, GluRδ2 and PSD-93 proteins were concentrated at the contacted portion of mismatched synapses, whereas AMPA receptors were distributed in both the contacted and dissociated portions. When GluRδ2 proteins were diminished, PC spines lost their synaptic contacts. We thus identified postsynaptic GluRδ2 as a key regulator of the presynaptic active zone and PSD organization at parallel fiber-PC synapses in the adult brain.