Synaptogenesis and synapse elimination

Formation of excess synaptic connections at perinatal stage and subsequent elimination of redundant synapses and strengthening of the surviving ones are crucial steps for functional neural circuit formation in developing nervous system. Shortly after birth, excitatory synapses are formed on the somata of Purkinje cells (PCs) from climbing fibers (CFs) that originate from neurons in the inferior olive of the contralateral medulla oblongata. At this developmental stage, each PC is innervated by multiple (around five) CFs with equal strengths. Subsequently, a single CF is selectively strengthened relative to other CFs during the first postnatal week. Then, around postnatal day 9 (P9), only the strongest CF (“winner” CF) starts to extend its innervation to PC dendrites. On the other hand, synapses of the weaker CFs (“loser” CFs) remain on the soma and the most proximal portion of the dendrite, and they are eliminated progressively during the second and the third postnatal weeks. From P6 to P11, the elimination proceeds independently of the formation of the synapses on PC dendrites from parallel fibers (PFs), the other excitatory inputs to PCs. From P12 and thereafter, the elimination of weaker CFs requires normal PF-PC synapse formation and is presumably dependent on the PF synaptic inputs that activate type 1 metabotropic glutamate receptor (mGluR1) and its downstream signaling in PCs. Most PCs become mono-innervated by single CFs in the third postnatal week. This chapter integrates the current knowledge of synaptogenesis and subsequent synapse elimination at CF to PC connections during postnatal cerebellar development.