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

C. E. Andreescu, F. Prestori, F. Brandalise, A. D'Errico, M. T G De Jeu, P. Rossi, L. Botta, G. Kohr, P. Perin, E. D'Angelo, C. I. De Zeeuw

Research output: Contribution to journalArticlepeer-review

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 (NR2AδC/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.

Original languageEnglish
Pages (from-to)274-283
Number of pages10
JournalNeuroscience
Volume176
DOIs
Publication statusPublished - Mar 10 2011

Keywords

  • Behavior
  • LTP
  • Motor learning
  • NMDA receptor
  • Plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this