title: Cdk5/p35 is required for motor coordination and cerebellar plasticity.
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.
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: He
authors.forename: Masato
authors.initials: M
authors.lastname: Ishizeki
authors.forename: Naoki
authors.initials: N
authors.lastname: Mita
authors.forename: Seitaro
authors.initials: S
authors.lastname: Wada
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Araki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ogura
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D010770:Phosphotransferases / Q000172:deficiency* / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology*
chemical_list: C492236:Cdk5r1 protein, mouse; D010770:Phosphotransferases
keywords: long-term synaptic plasticity; motor learning; rota-rod