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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 (NR2AC/C 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 NMDANR2A
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
