Tomonori Takeuchi

Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking delphilin

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Tomonori Takeuchi
  • Gen Ohtsuki
  • ,
  • Takashi Yoshida
  • ,
  • Masahiro Fukaya
  • ,
  • Tasuku Wainai
  • ,
  • Manami Yamashita
  • ,
  • Yoshito Yamazaki
  • ,
  • Hisashi Mori
  • ,
  • Kenji Sakimura
  • ,
  • Susumu Kawamoto
  • ,
  • Masahiko Watanabe
  • ,
  • Tomoo Hirano
  • ,
  • Masayoshi Mishina

In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) delta2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRdelta2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRdelta2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca(2+) required for the induction of LTD appeared to be reduced in the mutant mice, while Ca(2+) influx through voltage-gated Ca(2+) channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR) was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning.

Original languageEnglish
JournalPLOS ONE
Volume3
Issue5
Pages (from-to)e2297
ISSN1932-6203
DOIs
Publication statusPublished - 28 May 2008

    Research areas

  • Adaptation, Physiological/genetics, Animals, Base Sequence, Blotting, Western, Cerebellum/anatomy & histology, DNA Primers, Excitatory Postsynaptic Potentials, Eye Movements, Long-Term Synaptic Depression/genetics, Male, Mice, Mice, Knockout, Mice, Mutant Strains, Nerve Tissue Proteins/genetics, Receptors, AMPA/metabolism

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