Journal
CEREBRAL CORTEX
Volume 26, Issue 5, Pages 2084-2092Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhv031
Keywords
Fragile X; LTP; mGlu receptor; NMDA receptor; synaptic plasticity
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Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- L'Agence nationale de la Recherche (ANR) Blanc France-Taiwan RescueMemo
- ANR CYFIP-Aut
- FRAXA Research Foundation
- NARSAD
- Foundation Jerome Lejeune
- Alzheimers Research UK [ARUK-SRF2012-6] Funding Source: researchfish
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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 mGlus 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.
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