Tomonori Takeuchi

Ablation of glutamate receptor GluRδ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory

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  • Taisuke Miyazaki, Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
  • ,
  • Miwako Yamasaki
  • ,
  • Tomonori Takeuchi
  • Kenji Sakimura
  • ,
  • Masayoshi Mishina
  • ,
  • Masahiko Watanabe

Glutamate receptor GluRδ2 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 GluRδ2 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 GluRδ2 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 GluRδ2 ablation, and increased progressively both in number and amplitude. Therefore, GluRδ2 is essential for maintaining CF monoinnervation in adult cerebellum by suppressing aberrant invasion of CF branches to the territory of PF innervation. Thus, GluRδ2 fuels heterosynaptic competition and gives PFs the competitive advantages over CFs throughout the animal's life.

Original languageEnglish
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Pages (from-to)15196-209
Number of pages14
Publication statusPublished - 10 Nov 2010

    Research areas

  • Analysis of Variance, Animals, Cerebellum/cytology, Dendrites/physiology, Electrophysiology, Mice, Mice, Knockout, Motor Skills/physiology, Nerve Fibers/physiology, Nerve Net/physiology, Neuronal Tract-Tracers, Purkinje Cells/cytology, Receptors, AMPA/genetics, Rotarod Performance Test, Statistics, Nonparametric, Synapses/physiology

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