Developmental Alterations in Inhibitory Neurotransmission in the Fragile X Syndrome Mouse Basolateral Amygdala

Abstract

Fragile X Syndrome, caused by Fmr1 gene inactivation, is characterized by symptoms including enhanced fear, hyperactivity, social anxiety, and autism, pointing to synaptic and neural circuit defects in the amygdala. Previous studies in Fmr1 knockout (KO) mice have demonstrated alterations in GABAA receptor (GABAAR) function in the basolateral amygdala during early postnatal development. In this study, we sought to determine whether these early defects in GABAAR function are accompanied by changes in protein expression of GABAAR alpha 1, 2, and 3 subunits, the pre-synaptic GABA-synthesizing proteins GAD65 and 67 (GAD65/67), and the post-synaptic GABAAR-clustering protein gephyrin. We found that the developmental trajectory of protein expression is altered in knockout mice for all tested proteins except GABAAR alpha 3 and GAD 65/67. Our results suggest that alterations in the timing of inhibitory synapse protein expression in early postnatal development could contribute to observed inhibitory neurotransmission deficits in the KO mouse basolateral amygdala.