Molecular mechanisms for competitive synaptic wiring in cerebellar Purlfinje cells

点击翻译按钮获取中文摘要

Innervation of cerebellar Purkinje cells (PCs) by parallel fibers (PFs) and climbing fibers (CFs) is one of the best model system for synaptic circuit development and maturation. Through our previous analysis on PF synapse-specific molecule GluRd2, we have shown that this molecule strengthens synaptogenesis by PFs. Without GluRd2, PF-PCPC synapses are markedly reduced in number, and many PC spines on distal dendrites became free of synaptic contact (Kurihara et al.,1997, J.Neurosci.17:9613-9623). In this research project, we aimed to clarify what happens for CF in nervation under weakened PF synaptogenesis. By employing anterograde tracer labeling and immunolabeling, distal extension of CF in nervation was shown to occur in GluRd2 knockout mice and innervated free spines on distal dendrites of the PC. The distal extension further occurred against distal dendrites on adjacent PCs, resulting in multiple CF in nervation (Hahimoto et al.,2001;J.Neurosci.21:9701-9712 ; Ichikawa et al.,2002, J.Neurosci.22:8487-8503). These results indicate that synaptogenesis on PC dendrites stands on active competition between PF and CF, in which GluRd2 strengthens PF innervation to distal dendrites. Furthermore, we further revealed that P/Q-type calcium channel alpha-1A, which is activated by CF and induces calcium influx to PC dendrites, is the molecular mechanism that strengthens in nervation by a single major CF at proximal dendrites and expels other lesser CFs and PFs from the dendrites (Miyazaki et al.,2004, J.Neurosci.24:1734-1743).