Climbing fiber synapse elimination in cerebellar Purkinje cells

Innervation of Purkinje cells (PCs) by multiple climbing fibers (CFs) is refined into mono-innervation during the first three postnatal weeks of rodents lives. In this review article, we will integrate the current knowledge on developmental process and mechanisms of CF synapse elimination. In the creeper stage of CF innervation (postnatal day 0 (P0)similar to), CFs creep among PC somata to form transient synapses on immature dendrites. In the pericellular nest stage (P5 similar to), CFs densely surround and innervate PC somata. CF innervation is then displaced to the apical portion of PC somata in the capuchon stage (P9 similar to), and translocate to dendrites in the dendritic (P12 similar to) stage. Along with the developmental changes in CF wiring, functional and morphological distinctions become larger among CF inputs. PCs are initially innervated by more than five CFs with similar strengths (similar to P3). During P37 only a single CF is selectively strengthened (functional differentiation), and it undergoes dendritic translocation from P9 on (dendritic translocation). Following the functional differentiation, perisomatic CF synapses are eliminated nonselectively; this proceeds in two distinct phases. The early phase (P711) is conducted independently of parallel fiber (PF)PC synapse formation, while the late phase (P1217) critically depends on it. The P/Q-type voltage-dependent Ca2+ channel in PCs triggers selective strengthening of single CF inputs, promotes dendritic translocation of the strengthened CFs, and drives the early phase of CF synapse elimination. In contrast, the late phase is mediated by the mGluR1GaqPLC beta 4PKC signaling cascade in PCs driven at PFPC synapses, whose structural connectivity is stabilized and maintained by the GluRd2Cbln1neurexin system.