---
_id: '746'
abstract:
- lang: eng
text: Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated
in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at
the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored.
Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5
cell-surface mobility, synaptic N-methyl-D-Aspartate receptor (NMDAR) function,
and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using
single-molecule tracking, we found that mGluR5 was significantly more mobile at
synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface
co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of
synaptic NMDAR currents, a lack of their mGluR5-Activated long-Term depression,
and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral
phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides
a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes
of FXS, unveiling novel targets for mGluR5-based therapeutics.
article_number: '1103'
article_processing_charge: No
author:
- first_name: Elisabetta
full_name: Aloisi, Elisabetta
last_name: Aloisi
- first_name: Katy
full_name: Le Corf, Katy
last_name: Le Corf
- first_name: Julien
full_name: Dupuis, Julien
last_name: Dupuis
- first_name: Pei
full_name: Zhang, Pei
last_name: Zhang
- first_name: Melanie
full_name: Ginger, Melanie
last_name: Ginger
- first_name: Virginie
full_name: Labrousse, Virginie
last_name: Labrousse
- first_name: Michela
full_name: Spatuzza, Michela
last_name: Spatuzza
- first_name: Matthias
full_name: Georg Haberl, Matthias
last_name: Georg Haberl
- first_name: Lara
full_name: Costa, Lara
last_name: Costa
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Anke
full_name: Tappe Theodor, Anke
last_name: Tappe Theodor
- first_name: Fillippo
full_name: Drago, Fillippo
last_name: Drago
- first_name: Pier
full_name: Vincenzo Piazza, Pier
last_name: Vincenzo Piazza
- first_name: Christophe
full_name: Mulle, Christophe
last_name: Mulle
- first_name: Laurent
full_name: Groc, Laurent
last_name: Groc
- first_name: Lucia
full_name: Ciranna, Lucia
last_name: Ciranna
- first_name: Maria
full_name: Catania, Maria
last_name: Catania
- first_name: Andreas
full_name: Frick, Andreas
last_name: Frick
citation:
ama: Aloisi E, Le Corf K, Dupuis J, et al. Altered surface mGluR5 dynamics provoke
synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice. Nature
Communications. 2017;8(1). doi:10.1038/s41467-017-01191-2
apa: Aloisi, E., Le Corf, K., Dupuis, J., Zhang, P., Ginger, M., Labrousse, V.,
… Frick, A. (2017). Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction
and cognitive defects in Fmr1 knockout mice. Nature Communications. Nature
Publishing Group. https://doi.org/10.1038/s41467-017-01191-2
chicago: Aloisi, Elisabetta, Katy Le Corf, Julien Dupuis, Pei Zhang, Melanie Ginger,
Virginie Labrousse, Michela Spatuzza, et al. “Altered Surface MGluR5 Dynamics
Provoke Synaptic NMDAR Dysfunction and Cognitive Defects in Fmr1 Knockout Mice.”
Nature Communications. Nature Publishing Group, 2017. https://doi.org/10.1038/s41467-017-01191-2.
ieee: E. Aloisi et al., “Altered surface mGluR5 dynamics provoke synaptic
NMDAR dysfunction and cognitive defects in Fmr1 knockout mice,” Nature Communications,
vol. 8, no. 1. Nature Publishing Group, 2017.
ista: Aloisi E, Le Corf K, Dupuis J, Zhang P, Ginger M, Labrousse V, Spatuzza M,
Georg Haberl M, Costa L, Shigemoto R, Tappe Theodor A, Drago F, Vincenzo Piazza
P, Mulle C, Groc L, Ciranna L, Catania M, Frick A. 2017. Altered surface mGluR5
dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout
mice. Nature Communications. 8(1), 1103.
mla: Aloisi, Elisabetta, et al. “Altered Surface MGluR5 Dynamics Provoke Synaptic
NMDAR Dysfunction and Cognitive Defects in Fmr1 Knockout Mice.” Nature Communications,
vol. 8, no. 1, 1103, Nature Publishing Group, 2017, doi:10.1038/s41467-017-01191-2.
short: E. Aloisi, K. Le Corf, J. Dupuis, P. Zhang, M. Ginger, V. Labrousse, M. Spatuzza,
M. Georg Haberl, L. Costa, R. Shigemoto, A. Tappe Theodor, F. Drago, P. Vincenzo
Piazza, C. Mulle, L. Groc, L. Ciranna, M. Catania, A. Frick, Nature Communications
8 (2017).
date_created: 2018-12-11T11:48:17Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2023-09-27T12:27:30Z
day: '01'
ddc:
- '571'
department:
- _id: RySh
doi: 10.1038/s41467-017-01191-2
external_id:
isi:
- '000413571300004'
file:
- access_level: open_access
checksum: 99ceee57549dc0461e3adfc037ec70a9
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:32Z
date_updated: 2020-07-14T12:47:58Z
file_id: '5287'
file_name: IST-2017-915-v1+1_s41467-017-01191-2.pdf
file_size: 1841650
relation: main_file
file_date_updated: 2020-07-14T12:47:58Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
issue: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
issn:
- '20411723'
publication_status: published
publisher: Nature Publishing Group
publist_id: '6921'
pubrep_id: '915'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive
defects in Fmr1 knockout mice
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 8
year: '2017'
...