title: Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning.
abstract: 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.
authors.affiliation: Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schonewille
authors.forename: A
authors.initials: A
authors.lastname: Belmeguenai
authors.forename: S K
authors.initials: SK
authors.lastname: Koekkoek
authors.forename: S H
authors.initials: SH
authors.lastname: Houtman
authors.forename: H J
authors.initials: HJ
authors.lastname: Boele
authors.forename: B J
authors.initials: BJ
authors.lastname: van Beugen
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.forename: A
authors.initials: A
authors.lastname: Badura
authors.forename: G
authors.initials: G
authors.lastname: Ohtsuki
authors.forename: W E
authors.initials: WE
authors.lastname: Amerika
authors.forename: E
authors.initials: E
authors.lastname: Hosy
authors.forename: F E
authors.initials: FE
authors.lastname: Hoebeek
authors.forename: Y
authors.initials: Y
authors.lastname: Elgersma
authors.forename: C
authors.initials: C
authors.lastname: Hansel
authors.forename: C I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D003215:Conditioning, Eyelid / Q000502:physiology; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D013997:Time Factors
chemical_list: D019703:Calcineurin
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