Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galpha q

Abstract

Mice lacking the alpha -subunit of the heterotrimeric guanine nucleotide binding protein Gq (Galpha q) are viable but suffer from ataxia with typical signs of motor discoordination. The anatomy of the cerebellum is not overtly disturbed, and excitatory synaptic transmission from parallel fibers to cerebellar Purkinje cells (PCs) and from climbing fibers (CFs) to PCs is functional. However, about 40% of adult Galpha q mutant PCs remain multiply innervated by CFs because of a defect in regression of supernumerary CFs in the third postnatal week. Evidence is provided suggesting that Galpha q is part of a signaling pathway that is involved in the elimination of multiple CF innervation during this period.

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© 1997 by the National Academy of Sciences Contributed by Melvin I. Simon, October 6, 1997 S.O and K.H. contributed equally to this work. We thank S. Pease, V. Mancino, Y.-H. Hu, and J. Silva for expert technical help and Dr. Jeansok J. Kim for help with the behavioral experiments. S.O. was a recipient of a fellowship from the Deutsche Forschungsgemeinschaft and the Guenther Foundation. This work has been partly supported by grants to M.K. from the Japanese Ministry of Education, Science, and Culture, by CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST), and by a grant from the National Institutes of Health to M.I.S. 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.

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