title: NR2A subunit of the N-methyl D-aspartate receptors are required for potentiation at the mossy fiber to granule cell synapse and vestibulo-cerebellar motor learning.
abstract: Traditionally studies aimed at elucidating the molecular mechanisms underlying cerebellar motor learning have been focused on plasticity at the parallel fiber to Purkinje cell synapse. In recent years, however, the concept is emerging that formation and storage of memories are both distributed over multiple types of synapses at different sites. Here, we examined the potential role of potentiation at the mossy fiber to granule cell synapse, which occurs upstream to plasticity in Purkinje cells. We show that null-mutants of N-methyl d-aspartate-NR2A receptors (NMDA-NR2A(-/-) mice) have impaired induction of postsynaptic long-term potentiation (LTP) at the mossy fiber terminals and a reduced ability to raise the granule cell synaptic excitation, while the basic excitatory output of the mossy fibers is unaffected. In addition, we demonstrate that these NR2A(-/-) mutants as well as mutants in which the C terminal in the NR2A subunit is selectively truncated (NR2A(ΔC/ΔC) mice) have deficits in phase reversal adaptation of their vestibulo-ocular reflex (VOR), while their basic eye movement performance is similar to that of wild type littermates. These results indicate that NMDA-NR2A mediated potentiation at the mossy fiber to granule cell synapse is not required for basic motor performance, and they raise the possibility that it may contribute to some forms of vestibulo-cerebellar memory formation.
authors.affiliation: Department of Neuroscience, Erasmus MC, Dr. Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: Andreescu
authors.forename: F
authors.initials: F
authors.lastname: Prestori
authors.forename: F
authors.initials: F
authors.lastname: Brandalise
authors.forename: A
authors.initials: A
authors.lastname: D'Errico
authors.forename: M T G
authors.initials: MT
authors.lastname: De Jeu
authors.forename: P
authors.initials: P
authors.lastname: Rossi
authors.forename: L
authors.initials: L
authors.lastname: Botta
authors.forename: G
authors.initials: G
authors.lastname: Kohr
authors.forename: P
authors.initials: P
authors.lastname: Perin
authors.forename: E
authors.initials: E
authors.lastname: D'Angelo
authors.forename: C I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000818:Animals; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology*; D009412:Nerve Fibers / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: C120997:NR2A NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate