title: Motor Learning Requires Purkinje Cell Synaptic Potentiation through Activation of AMPA-Receptor Subunit GluA3.
abstract: Accumulating evidence indicates that cerebellar long-term potentiation (LTP) is necessary for procedural learning. However, little is known about its underlying molecular mechanisms. Whereas AMPA receptor (AMPAR) subunit rules for synaptic plasticity have been extensively studied in relation to declarative learning, it is unclear whether these rules apply to cerebellum-dependent motor learning. Here we show that LTP at the parallel-fiber-to-Purkinje-cell synapse and adaptation of the vestibulo-ocular reflex depend not on GluA1- but on GluA3-containing AMPARs. In contrast to the classic form of LTP implicated in declarative memory formation, this form of LTP does not require GluA1-AMPAR trafficking but rather requires changes in open-channel probability of GluA3-AMPARs mediated by cAMP signaling and activation of the protein directly activated by cAMP (Epac). We conclude that vestibulo-cerebellar motor learning is the first form of memory acquisition shown to depend on GluA3-dependent synaptic potentiation by increasing single-channel conductance.
authors.affiliation: Synaptic Plasticity and Behavior Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands; Cerebellar Coordination and Cognition Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands; Department of Neuroscience, Erasmus MC Rotterdam, 3015 GE Rotterdam, the Netherlands.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gutierrez-Castellanos
authors.affiliation: Synaptic Plasticity and Behavior Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands; Cerebellar Coordination and Cognition Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Da Silva-Matos
authors.affiliation: Department of Neuroscience, Erasmus MC Rotterdam, 3015 GE Rotterdam, the Netherlands.
authors.forename: Kuikui
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Cerebellar Coordination and Cognition Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands.
authors.forename: Cathrin B
authors.initials: CB
authors.lastname: Canto
authors.affiliation: Synaptic Plasticity and Behavior Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Renner
authors.affiliation: Synaptic Plasticity and Behavior Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands.
authors.forename: Linda M C
authors.initials: LMC
authors.lastname: Koene
authors.affiliation: Cerebellar Coordination and Cognition Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands.
authors.forename: Ozgecan
authors.initials: O
authors.lastname: Ozyildirim
authors.affiliation: Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.affiliation: Synaptic Plasticity and Behavior Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands. Electronic address: h.kessels@nin.knaw.nl.
authors.forename: Helmut W
authors.initials: HW
authors.lastname: Kessels
authors.affiliation: Cerebellar Coordination and Cognition Group, The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, the Netherlands; Department of Neuroscience, Erasmus MC Rotterdam, 3015 GE Rotterdam, the Netherlands.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D053483:Eye Movement Measurements; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D036881:Long-Term Synaptic Depression / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D018091:Receptors, AMPA / Q000235:genetics*
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3
keywords: AMPA receptor; Epac; GluA3; LTP; Purkinje cell; cerebellum; learning; synapse