Fragile X syndrome (FXS) is a neurodevelopmental disorder (NDD) characterized by intellectual disability, autism spectrum disorders (ASDs), and anxiety disorders. The disruption in the function of the FMR1 gene results in a range of alterations in cellular and synaptic function. Previous studies have identified dynamic alterations in inhibitory neurotransmission in early postnatal development in the amygdala of the mouse model of FXS. However, little is known about how these changes alter

more »

... ircuit development and plasticity in the lateral amygdala (LA). Using whole-cell patch clamp electrophysiology, we demonstrate that principal neurons (PNs) in the LA exhibit hyperexcitability with a concomitant increase in the synaptic strength of excitatory synapses in the BLA. Further, reduced feed-forward inhibition appears to enhance synaptic plasticity in the FXS amygdala. These results demonstrate that plasticity is enhanced in the amygdala of the juvenile Fmr1 knockout (KO) mouse and that E/I imbalance may underpin anxiety disorders commonly seen in FXS and ASDs. These studies identify significant cellular and synaptic defects in a behaviorally-relevant brain to the pathology of fragile X syndrome (FXS). We find that principal neurons (PNs) in the FXS basolateral amygdala (BLA) exhibit marked hyperexcitability as early as P21. Further, we show that feed-forward inhibition is reduced in the Fmr1 knock-out (KO) LA. This contributes to enhanced synaptic plasticity in LA of the Fmr1KO mouse.