Signal Transduction Cascade from mGluR1 to PKCγ Is Involved in Climbing Fiber Synapse Elimination During Postnatal Cerebellar Development

Abstract

Specific neuronal connections in the mature nervous system are considered to be established by elimination of redundant connections during development (Purves and Lichtman 1980). The climbing fiber (CF) system of the cerebellum has been a good model to study how mature and functional synaptic connections are formed during postnatal development. In the cerebellum of mature animals, each Purkinje cell (PC) is innervated by a single CF that originates from the inferior olive of the medulla and supplies strong excitatory synapses to proximal dendrites of PCs (Ito 1984). At early developmental stages, however, each PC is innervated by multiple CFs. Massive elimination of supernumerary CF synapses occurs postnatally, and the adult-type innervation pattern is established around P20 (Crepel 1982). Previous studies indicate that this developmental change of CF innervation requires the normal formation of excitatory synapses from parallel fibers (PFs), the other major excitatory inputs to PCs (Crepel 1982). However, molecular mechanisms of this developmental change have been largely unknown. Parallel fibers utilize L-Glu as their neurotransmitter (Ito 1984). Stimulation of PFs has been shown to activate both ionotropic AMPA receptors and the type 1 metabotropic glutamate receptor (mGluR1) on PC dendrites.