Cdk5/p35 is required for motor coordination and cerebellar plasticity

Xiaojuan He, Masato Ishizeki, Naoki Mita, Seitaro Wada, Yoshifumi Araki, Hiroo Ogura, Manabu Abe, Maya Yamazaki, Kenji Sakimura, Katsuhiko Mikoshiba, Takafumi Inoue, Toshio Ohshima

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Previous studies have implicated the role of Purkinje cells in motor learning and the underlying mechanisms have also been identified in great detail during the last decades. Here we report that cyclin-dependent kinase 5 (Cdk5)/p35 in Purkinje cell also contributes to synaptic plasticity. We previously showed that p35-/- (p35 KO) mice exhibited a subtle abnormality in brain structure and impaired spatial learning and memory. Further behavioral analysis showed that p35 KO mice had a motor coordination defect, suggesting that p35, one of the activators of Cdk5, together with Cdk5 may play an important role in cerebellar motor learning. Therefore, we created Purkinje cell-specific conditional Cdk5/p35 knockout (L7-p35 cKO) mice, analyzed the cerebellar histology and Purkinje cell morphology of these mice, evaluated their performance with balance beam and rota-rod test, and performed electrophysiological recordings to assess long-term synaptic plasticity. Our analyses showed that Purkinje cell-specific deletion of Cdk5/p35 resulted in no changes in Purkinje cell morphology but severely impaired motor coordination. Furthermore, disrupted cerebellar long-term synaptic plasticity was observed at the parallel fiber-Purkinje cell synapse in L7-p35 cKO mice. These results indicate that Cdk5/p35 is required for motor learning and involved in long-term synaptic plasticity.

Original languageEnglish
Pages (from-to)53-64
Number of pages12
JournalJournal of neurochemistry
Volume131
Issue number1
DOIs
Publication statusPublished - 2014 Oct

Keywords

  • long-term synaptic plasticity
  • motor learning
  • rota-rod

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    He, X., Ishizeki, M., Mita, N., Wada, S., Araki, Y., Ogura, H., Abe, M., Yamazaki, M., Sakimura, K., Mikoshiba, K., Inoue, T., & Ohshima, T. (2014). Cdk5/p35 is required for motor coordination and cerebellar plasticity. Journal of neurochemistry, 131(1), 53-64. https://doi.org/10.1111/jnc.12756