Basolateral Amygdala Hyperexcitability is Associated With Precocious Developmental Emergence of Fear-Learning in Fragile X Syndrome

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the most common monogenic cause of intellectual disability, autism spectrum disorders (ASDs) and anxiety disorders. Loss of fragile x mental retardation protein (FMRP) results in disruptions of synaptic development during a critical period (CP) of circuit formation in the basolateral amygdala (BLA). However, it is unknown how these alterations impact microcircuit development and function. Using a combination of electrophysiologic and behavioral approaches, we demonstrate that principal neurons (PNs) in the Fmr1KO BLA exhibit hyperexcitability during a sensitive period in amygdala development. This hyperexcitability contributes to increased excitatory gain in fear-learning circuits. Further, synaptic plasticity is enhanced in the BLA ofFmr1KO mice. Behavioral correlation demonstrates that fear-learning emerges precociously in the Fmr1KO mouse.  These results suggest that CP plasticity in the amygdala of the Fmr1KO mouse may be shifted to earlier developmental timepoints.