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Publication : Ablation of glutamate receptor GluRΓ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory.

First Author  Miyazaki T Year  2010
Journal  J Neurosci Volume  30
Issue  45 Pages  15196-209
PubMed ID  21068325 Mgi Jnum  J:166450
Mgi Id  MGI:4845794 Doi  10.1523/JNEUROSCI.0934-10.2010
Citation  Miyazaki T, et al. (2010) Ablation of glutamate receptor GluRdelta2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory. J Neurosci 30(45):15196-209
abstractText  Glutamate receptor GluRdelta2 is exclusively expressed in Purkinje cells (PCs) from early development and plays key roles in parallel fiber (PF) synapse formation, elimination of surplus climbing fibers (CFs), long-term depression, motor coordination, and motor learning. To address its role in adulthood, we previously developed a mouse model of drug-induced GluRdelta2 ablation in adult PCs (Takeuchi et al., 2005). In that study, we demonstrated an essential role to maintain the connectivity of PF-PC synapses, based on the observation that both mismatching of presynaptic and postsynaptic specializations and disconnection of PF-PC synapses are progressively increased after GluRdelta2 ablation. Here, we pursued its role for CF wiring in adult cerebellum. In parallel with the disconnection of PF-PC synapses, ascending CF branches exhibited distal extension to innervate distal dendrites of the target and neighboring PCs. Furthermore, transverse CF branches, a short motile collateral rarely forming synapses in wild-type animals, displayed aberrant mediolateral extension to innervate distal dendrites of neighboring and remote PCs. Consequently, many PCs were wired by single main CF and other surplus CFs innervating a small part of distal dendrites. Electrophysiological recording further revealed that surplus CF-EPSCs characterized with slow rise time and small amplitude emerged after GluRdelta2 ablation, and increased progressively both in number and amplitude. Therefore, GluRdelta2 is essential for maintaining CF monoinnervation in adult cerebellum by suppressing aberrant invasion of CF branches to the territory of PF innervation. Thus, GluRdelta2 fuels heterosynaptic competition and gives PFs the competitive advantages over CFs throughout the animal's life.
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