eprintid: 10057901
rev_number: 20
eprint_status: archive
userid: 608
dir: disk0/10/05/79/01
datestamp: 2018-10-10 10:34:40
lastmod: 2021-09-19 22:21:42
status_changed: 2018-10-10 10:34:40
type: article
metadata_visibility: show
creators_name: Kellermayer, B
creators_name: Ferreira, JS
creators_name: Dupuis, J
creators_name: Levet, F
creators_name: Grillo-Bosch, D
creators_name: Bard, L
creators_name: Linarès-Loyez, J
creators_name: Bouchet, D
creators_name: Choquet, D
creators_name: Rusakov, DA
creators_name: Bon, P
creators_name: Sibarita, J-B
creators_name: Cognet, L
creators_name: Sainlos, M
creators_name: Carvalho, AL
creators_name: Groc, L
title: Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F81
keywords: glutamate receptor, dSTORM, single molecule, GluN2 subunit, synapse
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: NMDA receptors (NMDARs) play key roles in the use-dependent adaptation of glutamatergic synapses underpinning memory formation. In the forebrain, these plastic processes involve the varied contributions of GluN2A- and GluN2B-containing NMDARs that have different signaling properties. Although the molecular machinery of synaptic NMDAR trafficking has been under scrutiny, the postsynaptic spatial organization of these two receptor subtypes has remained elusive. Here, we used super-resolution imaging of NMDARs in rat hippocampal synapses to unveil the nanoscale topography of native GluN2A- and GluN2B-NMDARs. Both subtypes were found to be organized in separate nanodomains that vary over the course of development. Furthermore, GluN2A- and GluN2B-NMDAR nanoscale organizations relied on distinct regulatory mechanisms. Strikingly, the selective rearrangement of GluN2A- and GluN2B-NMDARs, with no overall change in NMDAR current amplitude, allowed bi-directional tuning of synaptic LTP. Thus, GluN2A- and GluN2B-NMDAR nanoscale organizations are differentially regulated and seem to involve distinct signaling complexes during synaptic adaptation.
date: 2018-10-10
date_type: published
official_url: https://doi.org/10.1016/j.neuron.2018.09.012
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1590303
doi: 10.1016/j.neuron.2018.09.012
pii: S0896-6273(18)30785-2
language_elements: English
lyricists_name: Rusakov, Dmitri
lyricists_id: DRUSA01
actors_name: Rusakov, Dmitri
actors_id: DRUSA01
actors_role: owner
full_text_status: public
publication: Neuron
volume: 100
pagerange: 1-14
event_location: United States
issn: 0896-6273
citation:        Kellermayer, B;    Ferreira, JS;    Dupuis, J;    Levet, F;    Grillo-Bosch, D;    Bard, L;    Linarès-Loyez, J;                                     ... Groc, L; + view all <#>        Kellermayer, B;  Ferreira, JS;  Dupuis, J;  Levet, F;  Grillo-Bosch, D;  Bard, L;  Linarès-Loyez, J;  Bouchet, D;  Choquet, D;  Rusakov, DA;  Bon, P;  Sibarita, J-B;  Cognet, L;  Sainlos, M;  Carvalho, AL;  Groc, L;   - view fewer <#>    (2018)    Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses.                   Neuron , 100    pp. 1-14.    10.1016/j.neuron.2018.09.012 <https://doi.org/10.1016/j.neuron.2018.09.012>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10057901/1/Rusakov_Differential%20Nanoscale%20Topography%20and%20Functional%20Role%20of%20GluN2-NMDA%20Receptor%20Subtypes%20at%20Glutamatergic%20Synapses_AAM.pdf