Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning.

M. Schonewille, A. Belmeguenai, S.K. Koekkoek, S.H. Houtman, H.J. Boele, B.J. van Beugen, Z. Gao, A. Badura, G. Ohtsuki, W.E. Amerika, E. Hosy, F.E. Hoebeek, Y. Elgersma, C. Hansel, C.I. De Zeeuw
Neuron. 2010-08-01; 67(4): 618-628
DOI: 10.1016/j.neuron.2010.07.009

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1. Neuron. 2010 Aug 26;67(4):618-28. doi: 10.1016/j.neuron.2010.07.009.

Purkinje cell-specific knockout of the protein phosphatase PP2B impairs
potentiation and cerebellar motor learning.

Schonewille M(1), Belmeguenai A, Koekkoek SK, Houtman SH, Boele HJ, van Beugen
BJ, Gao Z, Badura A, Ohtsuki G, Amerika WE, Hosy E, Hoebeek FE, Elgersma Y,
Hansel C, De Zeeuw CI.

Author information:
(1)Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands.

Comment in
Neuron. 2010 Aug 26;67(4):525-6.

Cerebellar motor learning is required to obtain procedural skills. Studies have
provided supportive evidence for a potential role of kinase-mediated long-term
depression (LTD) at the parallel fiber to Purkinje cell synapse in cerebellar
learning. Recently, phosphatases have been implicated in the induction of
potentiation of Purkinje cell activities in vitro, but it remains to be shown
whether and how phosphatase-mediated potentiation contributes to motor learning.
Here, we investigated its possible role by creating and testing a Purkinje
cell-specific knockout of calcium/calmodulin-activated protein-phosphatase-2B
(L7-PP2B). The selective deletion of PP2B indeed abolished postsynaptic long-term
potentiation in Purkinje cells and their ability to increase their excitability,
whereas LTD was unaffected. The mutants showed impaired “gain-decrease” and
“gain-increase” adaptation of their vestibulo-ocular reflex (VOR) as well as
impaired acquisition of classical delay conditioning of their eyeblink response.
Thus, our data indicate that PP2B may indeed mediate potentiation in Purkinje
cells and contribute prominently to cerebellar motor learning.

2010 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuron.2010.07.009
PMCID: PMC2941980
PMID: 20797538 [Indexed for MEDLINE]

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