1998•Proceedings of the National Academy of SciencesOpen access
Phospholipase Cβ4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum
Masanobu Kano, Kouichi Hashimoto, Masahiko Watanabe, Hideo Kurihara, Stefan Offermanns, Huiping Jiang, Yanping Wu, Kisun Jun, Hee‐Sup Shin, Yoshiro Inoue, Melvin I. Simon, Dianqing Wu
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Abstract
Elimination of excess climbing fiber (CF)-Purkinje cell synapses during cerebellar development involves a signaling pathway that includes type 1 metabotropic glutamate receptor, Galphaq, and the gamma isoform of protein kinase C. To identify phospholipase C (PLC) isoforms involved in this process, we generated mice deficient in PLCbeta4, one of two major isoforms expressed in Purkinje cells. PLCbeta4 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 PLCbeta4 mRNA is predominantly expressed. By contrast, CF synapse elimination is normal in the caudal cerebellum, in which low levels of PLCbeta4 mRNA but reciprocally high levels of PLCbeta3 mRNA are found. These results indicate that PLCbeta4 transduces signals that are required for CF synapse elimination in the rostral cerebellum.
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