Phospholipase Cβ4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum

Elimination of excess climbing fiber (CF)-Purkinje cell synapses during cerebellar development involves a signaling pathway that includes type 1 metabotropic glutamate receptor, G alpha q, and the gamma isoform of protein kinase C. To identify phospholipase C (PLC) isoforms involved in this process, we generated mice deficient in PLC beta 4, one of two major isoforms expressed in Purkinje cells. PLC beta 4 mutant mice are viable but exhibit locomotor ataxia. Their cerebellar histology, parallel fiber synapse formation, and basic electrophysiology appear normal. However, developmental elimination 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, in which low levels of PLC beta 4 mRNA but reciprocally high levels of PLC beta 3 mRNA are found. These results indicate that PLC beta 4 transduces signals that are required for CF synapse elimination in the rostral cerebellum.