Glutamate Receptor δ2 Subunit in Activity-Dependent Heterologous Synaptic Competition

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Abstract
In the adult cerebellum, the glutamate receptor δ2 subunit (GluRδ2) is selectively targeted to the spines of the distal Purkinje cell dendrites, the spiny branchlets, that are innervated by the parallel fibers. Although GluRδ2 has no known channel function, it is presumed to be involved in the formation and stabilization of these synapses. After block of electrical activity by tetrodotoxin, GluRδ2s appear in the postsynaptic densities of the proximal dendritic spines, which then lose their contact with climbing fibers and become ectopically innervated by parallel fibers. This phenomenon suggests that climbing fiber activity prevents GluRδ2 targeting to proximal dendrites and that GluRδ2s admitted to the postsynaptic density of the spine cause withdrawal of the silent climbing fiber. To test this hypothesis, we studied the distribution of GluRδ2s in the rat cerebellum by immunoelectron microscopy during the recovery period that follows removal of the electrical block, and during the sprouting of climbing fibers that follows subtotal deletion of the parent inferior olivary neurons by administration of the drug 3-acetylpyridine. We found that after removal of the electrical block, the climbing fibers reinnervate proximal spines that bear GluRδ2s and these subunits are successively repressed. Similarly, after subtotal lesion of the inferior olive, reinnervation of denervated Purkinje cells occurs on spines bearing GluRδ2s. Thus, GluRδ2s are not responsible for displacing silent climbing fibers. We propose instead that GluRδ2s are associated with climbing fiber-to-Purkinje cell synapses, during development or at early stages of climbing fiber regeneration or sprouting, and are downregulated during the process of synapse maturation.

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