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Linking NMDA Receptor Synaptic Retention to Synaptic Plasticity and Cognition

Lookup NU author(s): Dr Claudia Racca

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 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


Publication metadata

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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