Phospholipase C beta 4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum

Elimination of excess climbing fiber (CF)-Purkinje cell synapses during cer ebellar development involves a signaling pathway that includes type 1 metab otropic glutamate receptor, G alpha q, and the gamma isoform of protein kin ase C. To identify phospholipase C (PLC) isoforms involved in this process, we generated mice deficient in PLC beta 4, one of two major isoforms expre ssed in Purkinje cells. PLC beta 4 mutant mice are viable but exhibit locom otor ataxia. Their cerebellar histology, parallel fiber synapse formation, and basic electrophysiology appear normal. However, developmental eliminati on of multiple CF innervation clearly is impaired in the rostral portion of the cerebellar vermis, in which PLC beta 4 mRNA is predominantly expressed . By contrast, CF synapse elimination is normal in the caudal cerebellum, i n which low levels of PLC beta 4 mRNA but reciprocally high levels of PLC b eta 3 mRNA are found. These results indicate that PLC beta 4 transduces sig nals that are required for CF synapse elimination in the rostral cerebellum .