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Lookup NU author(s): Dr Claudia RaccaORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2019 The Author(s)NMDA receptor (NMDAR) subunit composition plays a pivotal role in synaptic plasticity at excitatory synapses. Still, the mechanisms responsible for the synaptic retention of NMDARs following induction of plasticity need to be fully elucidated. Rabphilin3A (Rph3A) is involved in the stabilization of NMDARs at synapses through the formation of a complex with GluN2A and PSD-95. Here we used different protocols to induce synaptic plasticity in the presence or absence of agents modulating Rph3A function. The use of Forskolin/Rolipram/Picrotoxin cocktail to induce chemical LTP led to synaptic accumulation of Rph3A and formation of synaptic GluN2A/Rph3A complex. Notably, Rph3A silencing or use of peptides interfering with the GluN2A/Rph3A complex blocked LTP induction. Moreover, in vivo disruption of GluN2A/Rph3A complex led to a profound alteration of spatial memory. Overall, our results demonstrate a molecular mechanism needed for NMDAR stabilization at synapses after plasticity induction and to trigger downstream signaling events necessary for cognitive behavior.© 2019 The Author(s)Molecular Interaction; Neuroscience; Molecular Neuroscience
Author(s): Franchini L, Stanic J, Ponzoni L, Mellone M, Carrano N, Musardo S, Zianni E, Olivero G, Marcello E, Pittaluga A, Sala M, Bellone C, Racca C, Di Luca M, Gardoni F
Publication type: Article
Publication status: Published
Journal: iScience
Year: 2019
Volume: 19
Pages: 927-939
Online publication date: 27/08/2019
Acceptance date: 21/08/2019
Date deposited: 22/08/2019
ISSN (electronic): 2589-0042
Publisher: Cell Press
URL: https://doi.org/10.1016/j.isci.2019.08.036
DOI: 10.1016/j.isci.2019.08.036
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