dc.contributor.author | Martin, HG | |
dc.contributor.author | Lassalle, O | |
dc.contributor.author | Brown, JT | |
dc.contributor.author | Manzoni, OJ | |
dc.date.accessioned | 2015-05-28T15:02:58Z | |
dc.date.issued | 2015-03-05 | |
dc.description.abstract | The most common inherited monogenetic cause of intellectual disability is Fragile X syndrome (FXS). The clinical symptoms of FXS evolve with age during adulthood; however, neurophysiological data exploring this phenomenon are limited. The Fmr1 knockout (Fmr1 KO) mouse models FXS, but studies in these mice of prefrontal cortex (PFC) function are underrepresented, and aging linked data are absent. We studied synaptic physiology and activity-dependent synaptic plasticity in the medial PFC of Fmr1 KO mice from 2 to 12 months. In young adult Fmr1 KO mice, NMDA receptor (NMDAR)-mediated long-term potentiation (LTP) is intact; however, in 12-month-old mice this LTP is impaired. In parallel, there was an increase in the AMPAR/NMDAR ratio and a concomitant decrease of synaptic NMDAR currents in 12-month-old Fmr1 KO mice. We found that acute pharmacological blockade of mGlu5 receptor in 12-month-old Fmr1 KO mice restored a normal AMPAR/NMDAR ratio and LTP. Taken together, the data reveal an age-dependent deficit in LTP in Fmr1 KO mice, which may correlate to some of the complex age-related deficits in FXS. | en_GB |
dc.description.sponsorship | Institut National de la Santé et de la Recherche Médicale (INSERM) | en_GB |
dc.description.sponsorship | L’Agence nationale de la Recherche (ANR) Blanc France-Taiwan Rescue Memo | en_GB |
dc.description.sponsorship | ANR CYFIP-Aut | en_GB |
dc.description.sponsorship | FRAXA Research Foundation | en_GB |
dc.description.sponsorship | NARSAD 2010 Independent Investigator Grant | en_GB |
dc.description.sponsorship | Foundation Jêrome Lejeune | en_GB |
dc.identifier.citation | Cerebral Cortex, 2015, 1-9 | en_GB |
dc.identifier.doi | 10.1093/cercor/bhv031 | |
dc.identifier.uri | http://hdl.handle.net/10871/17343 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/25750254 | en_GB |
dc.rights.embargoreason | Publisher's policy | en_GB |
dc.rights | © The Author 2015. Published by Oxford University Press. All rights reserved. | en_GB |
dc.subject | Fragile X | en_GB |
dc.subject | LTP | en_GB |
dc.subject | NMDA receptor | en_GB |
dc.subject | mGlu receptor | en_GB |
dc.subject | synaptic plasticity | en_GB |
dc.title | Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of the Fmr1 Knockout Mouse Model of Fragile X Syndrome. | en_GB |
dc.type | Article | en_GB |
dc.identifier.issn | 1047-3211 | |
dc.description | This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cerebral Cortex following peer review. The version of record is available online at: doi: 10.1093/cercor/bhv031. | en_GB |
dc.identifier.journal | Cerebral Cortex | en_GB |