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- W2994994002 abstract "markdownabstractThe hippocampus and the cerebellum are two different brain regions that encodedifferent types of memories. Whilst the hippocampus deals with declarativememory, the cerebellum is mainly involved in procedural memory. In the cerebellum, granule cells give rise to parallel fibers, which form synapticpoints with Purkinje cells - the parallel fiber-Purkinje cell synapse. We found fivemutations in cerebellar granule cell that did not affect phase reversal, a type ofcerebellar learning. However, in looking at Purkinje cells whose GluA3 subunit ofthe AMPA receptors was knocked out, we saw an impairment of phase reversaladaptation. We show, then, that the GluA3 AMPA receptor subunit is involvedin crucial cerebellar motor learning. We also show that this GluA3-mediatedmechanism defies some long-established rules regarding the potentiation of theparallel fiber-Purkinje cell synapse. In the hippocampus, learning depends on the trafficking of GluA1-containingAMPARs to synapses. GluA3-containing AMPARs, however, don’t seem tocontribute much to synaptic currents, synaptic plasticity or learning, thoughthey are present. We found that, in the hippocampus, the GluA3 subunit doesn’tcontribute to memory formation but does control memory retrieval. We see howthe effects of knocking out GluA3 reveal that the hippocampus AMPAR-mediatedrules for learning are opposite to the rules uncovered for the cerebellum regardingthe GluA1 and GluA3 subunits of the AMPA receptors. Lastly, we found that memories coded in the hippocampus are affected byamyloid-β, and that its effects occur through the removal of GluA3 from synapses.We demonstrate GluA3 subunit’s role in rendering the synapses susceptible toamyloid-β and how it requires PKCα phosphorylation of the GluA3 subunit atserine 885. We finally propose that Aβ causes synaptic deficits by corrupting theconstitutive cycling of GluA3-containing AMPA-receptors at synapses." @default.
- W2994994002 created "2019-12-26" @default.
- W2994994002 creator A5045546818 @default.
- W2994994002 date "2019-11-20" @default.
- W2994994002 modified "2023-09-23" @default.
- W2994994002 title "GluA3-Mediated Synaptic Plasticity and Dysfunction in the Cerebellum and in the Hippocampus: GluA3-gemedieerde synaptische plasticiteit en disfunctie in het cerebellum en hippocampus" @default.
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