Inhibition of GluN2A NMDA receptors ameliorates synaptic plasticity deficits in the Fmr1−/y mouse model

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp13211-list-0001">Fragile X syndrome (FXS) is a genetic condition that is the most common form of inherited intellectual impairment and causes a range of neurodevelopmental complications including learning disabilities and intellectual disability and shares many characteristics with autism spectrum disorder (ASD).In the FXS mouse model, Fmr1^−/y, impaired synaptic plasticity was restored by pharmacologically inhibiting GluN2A‐containing NMDA receptors but not GluN2B‐containing receptors.Similar results were obtained by crossing Fmr1^−/y with GluN2A knock‐out (Grin2A^−/−) mice.These results suggest that dampening the elevated levels of GluN2A‐containing NMDA receptors in Fmr1^−/y mice has the potential to restore hyperexcitability of the neural circuitry to (a more) normal‐like level of brain activity.