IMPAIRED PARALLEL FIBER-]PURKINJE CELL SYNAPSE STABILIZATION DURING CEREBELLAR DEVELOPMENT OF MUTANT MICE LACKING THE GLUTAMATE-RECEPTOR DELTA-2 SUBUNIT

The glutamate receptor delta 2 subunit (GluR delta 2) is specifically expressed in cerebellar Purkinje cells (PCs) from early developmental stages and is selectively localized at dendritic spines forming synaps es with parallel fibers (PFs). Targeted disruption of the GluR delta 2 gene leads to a significant reduction of PF-->PC synapses. To address its role in the synaptogenesis, the mor phology and electrophysiology of PF-->PC synapses were comparatively examined in developing GluR de lta 2 mutant and wildtype cerebella. PCs in GluR delta 2 mutant mice w ere normally produced, migrated, and formed spines, as did those in wi ldtype mice. At the end of the first postnatal week, 74-78% of PC spin es in both mice formed immature synapses, which were characterized by small synaptic contact, few synaptic vesicles, and incomplete surround ing by astroglial processes, eliciting little electrophysiological res ponse. During the second and third postnatal weeks when spines and ter minals are actively gener ated, the percentage of PC spines forming sy napses attained 98-99% in wild type but remained as low 55-60% in muta nts, and the rest were unattached to any nerve terminals. As a result, the number of PF synapses per single-mutant PCs was reduced to nearly a half-level of wild-type PCs. Parallelly, PF stimulation less effect ively elicited EPSCs in mutant PCs than in wild-type PCs during and af ter the second postnatal week. These results suggest that the GluR del ta 2 is involved in the stabilization and strengthening of synaptic co nnectivity between PFs and PCs, leading to the association of all PC s pines with PF terminals to form functionally mature synapses.