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.
KeywordsClimbing Fiber Postnatal Development Distal Dendrite Dendritic Compartment Synapse Elimination
This work has been supported in part by the Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior), Grants-in-Aid for Scientific Research 21220006 (M.K.) and 19100005 (M.W.), and the Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from MEXT, Japan.
- Altman J, Bayer SA (1997) Development of the cerebellar system: in relation to its evolution, structure, and functions. CRC Press, Boca RatonGoogle Scholar
- Cajal SR (1911) Histologie du systeme nerveux de l'homme et des vertebres, vol II. Maloine, ParisGoogle Scholar
- Hashimoto K, Watanabe M, Kurihara H, Offermanns S, Jiang H, Wu Y, Jun K, Shin HS, Inoue Y, Wu D, Simon MI, Kano M (2000) Climbing fiber synapse elimination during postnatal cerebellar development requires signal transduction involving Gαq and phospholipase C β4. Prog Brain Res 124:31–48PubMedCrossRefGoogle Scholar
- Hashimoto K, Ichikawa R, Takechi H, Inoue Y, Aiba A, Sakimura K, Mishina M, Hashikawa T, Konnerth A, Watanabe M, Kano M (2001) Roles of glutamate receptor δ2 subunit (GluRδ2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development. J Neurosci 21:9701–9712PubMedGoogle Scholar
- Ichikawa R, Miyazaki T, Kano M, Hashikawa T, Tatsumi H, Sakimura K, Mishina M, Inoue Y, Watanabe M (2002) Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor δ2. J Neurosci 22:8487–8503PubMedGoogle Scholar
- Ito M (1984) The cerebellum and neural control. Raven, New YorkGoogle Scholar
- Miyazaki T, Hashimoto K, Uda A, Sakagami H, Nakamura Y, Saito SY, Nishi M, Kume H, Tohgo A, Kaneko I, Kondo H, Fukunaga K, Kano M, Watanabe M, Takeshima H (2006) Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family. FEBS Lett 580:4057–4064PubMedCrossRefGoogle Scholar
- Miyazaki T, Yamasaki M, Takeuchi T, Sakimura K, Mishina M, Watanabe M (2010) Ablation of glutamate receptor GluRδ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory. J Neurosci 30:15196–15209PubMedCrossRefGoogle Scholar
- Rossi F, Wiklund L, van der Want JJ, Strata P (1991) Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses. J Comp Neurol 308:513–535PubMedCrossRefGoogle Scholar