Hyperexcitability and Loss of Feedforward Inhibition Contribute to Aberrant Plasticity in the Fmr1KO Amygdala.
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 microcircuit 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 knock-out (KO) mouse and that E/I imbalance may underpin anxiety disorders commonly seen in FXS and ASDs.
['Svalina|Matthew N|MN|0000-0001-9919-9053', 'Guthman|E Mae|EM|', 'Cea-Del Rio|Christian A|CA|', 'Kushner|J Keenan|JK|', 'Baca|Serapio M|SM|', 'Restrepo|Diego|D|', 'Huntsman|Molly M|MM|']
D000679:Amygdala D000818:Animals D004195:Disease Models, Animal D051860:Fragile X Mental Retardation Protein D005600:Fragile X Syndrome D051379:Mice D018345:Mice, Knockout D013569:Synapses D009435:Synaptic Transmission
fragile X syndrome lateral amygdala feed-forward inhibition synaptic plasticity E/I balance