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Cdk5/p35 is required for motor coordination and cerebellar plasticity
Article first published online: 28 MAY 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 131, Issue 1, pages 53–64, October 2014
How to Cite
J. Neurochem. (2014) 131, 53–64.
Cover Image for this issue: doi: 10.1111/jnc.12587.
- Issue published online: 24 SEP 2014
- Article first published online: 28 MAY 2014
- Accepted manuscript online: 7 MAY 2014 04:38AM EST
- Manuscript Accepted: 30 APR 2014
- Manuscript Revised: 27 MAR 2014
- Manuscript Received: 20 DEC 2013
- Ministry of Education, Culture, Sports, Science and Technology
- long-term synaptic plasticity;
- motor learning;
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.
Purkinje cells play an important role in motor learning, the underlying mechanisms of which have been studied during the last two decades. We report here that the ablation of Cdk5/p35 in Purkinje cells impairs motor coordination, along with deficits in the cerebellar synaptic plasticity, which gives new insights into the mechanism of synaptic plasticity in Purkinje cells.