{"scopus_import":"1","author":[{"full_name":"Aloisi, Elisabetta","last_name":"Aloisi","first_name":"Elisabetta"},{"first_name":"Katy","last_name":"Le Corf","full_name":"Le Corf, Katy"},{"full_name":"Dupuis, Julien","first_name":"Julien","last_name":"Dupuis"},{"full_name":"Zhang, Pei","first_name":"Pei","last_name":"Zhang"},{"first_name":"Melanie","last_name":"Ginger","full_name":"Ginger, Melanie"},{"full_name":"Labrousse, Virginie","first_name":"Virginie","last_name":"Labrousse"},{"full_name":"Spatuzza, Michela","last_name":"Spatuzza","first_name":"Michela"},{"full_name":"Georg Haberl, Matthias","last_name":"Georg Haberl","first_name":"Matthias"},{"first_name":"Lara","last_name":"Costa","full_name":"Costa, Lara"},{"last_name":"Shigemoto","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"full_name":"Tappe Theodor, Anke","first_name":"Anke","last_name":"Tappe Theodor"},{"last_name":"Drago","first_name":"Fillippo","full_name":"Drago, Fillippo"},{"first_name":"Pier","last_name":"Vincenzo Piazza","full_name":"Vincenzo Piazza, Pier"},{"last_name":"Mulle","first_name":"Christophe","full_name":"Mulle, Christophe"},{"full_name":"Groc, Laurent","last_name":"Groc","first_name":"Laurent"},{"first_name":"Lucia","last_name":"Ciranna","full_name":"Ciranna, Lucia"},{"full_name":"Catania, Maria","first_name":"Maria","last_name":"Catania"},{"last_name":"Frick","first_name":"Andreas","full_name":"Frick, Andreas"}],"publication":"Nature Communications","article_number":"1103","department":[{"_id":"RySh"}],"oa":1,"year":"2017","publication_status":"published","_id":"746","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"issue":"1","oa_version":"Published Version","external_id":{"isi":["000413571300004"]},"quality_controlled":"1","type":"journal_article","has_accepted_license":"1","day":"01","publisher":"Nature Publishing Group","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_size":1841650,"file_name":"IST-2017-915-v1+1_s41467-017-01191-2.pdf","checksum":"99ceee57549dc0461e3adfc037ec70a9","date_created":"2018-12-12T10:17:32Z","creator":"system","date_updated":"2020-07-14T12:47:58Z","file_id":"5287"}],"intvolume":"         8","publication_identifier":{"issn":["2041-1723"]},"date_updated":"2025-04-17T11:13:13Z","file_date_updated":"2020-07-14T12:47:58Z","license":"https://creativecommons.org/licenses/by/4.0/","language":[{"iso":"eng"}],"isi":1,"month":"12","ddc":["571"],"date_published":"2017-12-01T00:00:00Z","publist_id":"6921","volume":8,"abstract":[{"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.","lang":"eng"}],"title":"Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice","pubrep_id":"915","status":"public","doi":"10.1038/s41467-017-01191-2","article_processing_charge":"No","date_created":"2018-12-11T11:48:17Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}