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

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

^*Department of Physiology, Kanazawa University School of Medicine, Takara-machi, Kanazawa 920-8640, Japan; ^†Laboratory for Cellular Neurophysiology, Brain Science Institute, The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan; ^‡CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan; ^¶Department of Physiology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken 329-0498, Japan; ^‖Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan; ^**Division of Biology, California Institute of Technology, Pasadena, CA 91125; ^‡‡Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642-8711; and ^††National CRI Center for Calcium and Learning, and Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea

Contributed by Melvin I. Simon

Abstract

Elimination of excess climbing fiber (CF)–Purkinje cell synapses during cerebellar development involves a signaling pathway that includes type 1 metabotropic glutamate receptor, Gαq, and the γ isoform of protein kinase C. To identify phospholipase C (PLC) isoforms involved in this process, we generated mice deficient in PLCβ4, one of two major isoforms expressed in Purkinje cells. PLCβ4 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 PLCβ4 mRNA is predominantly expressed. By contrast, CF synapse elimination is normal in the caudal cerebellum, in which low levels of PLCβ4 mRNA but reciprocally high levels of PLCβ3 mRNA are found. These results indicate that PLCβ4 transduces signals that are required for CF synapse elimination in the rostral cerebellum.

Footnotes

↵ § To whom reprint requests should be addressed. e-mail: mkano{at}med.kanazawa-u.ac.jp.
‡‡ Present address: Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69-73 Berlin, Germany.
ABBREVIATIONS:

PC,

Purkinje cell;

mGluR1,

type 1 metabotropic glutamate receptor;

PLC,

phospholipase C;

PKC,

protein kinase C;

PF,

parallel fiber;

CF,

climbing fiber;

P21,

postnatal day 21;

EPSC,

excitatory postsynaptic current