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, Galpha q, and the gamma isoform of protein kinase C. To identify phospholipase C (PLC) isoforms involved in this process, we generated mice deficient in PLCbeta 4, one of two major isoforms expressed in Purkinje cells. PLCbeta 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 PLCbeta 4 mRNA is predominantly expressed. By contrast, CF synapse elimination is normal in the caudal cerebellum, in which low levels of PLCbeta 4 mRNA but reciprocally high levels of PLCbeta 3 mRNA are found. These results indicate that PLCbeta 4 transduces signals that are required for CF synapse elimination in the rostral cerebellum
Additional Information© 1998 by The National Academy of Sciences Contributed by Melvin I. Simon, October 12, 1998 We thank K. Matsumoto and V. Mancino for expert technical help and Dr. N. Kawai for continuous encouragement. This work has been supported by grants to M.K. from the Japanese Ministry of Education, Science, Sports and Culture, from the Human Frontier Science Program, and by Special Coordination Funds for promoting Science and Technology from the Science and Technology Agency of the Japanese Government. This work also has been supported by a grant to H.-S.S. from the Creative Research Initiatives of the Korean Government and by grants to D.W. and to M.I.S. from the National Institutes of Health. S.O. was a recipient of a fellowship from the Deutsche Forschungsgemeinschaft and the Guenther Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Published - KANpnas98.pdf