TY - JOUR T1 - Correction of amygdalar dysfunction in a rat model of fragile X syndrome. JF - Cell Rep Y1 - 2021 A1 - Fernandes, Giselle A1 - Mishra, Pradeep K A1 - Nawaz, Mohammad Sarfaraz A1 - Donlin-Asp, Paul G A1 - Rahman, Mohammed Mostafizur A1 - Hazra, Anupam A1 - Kedia, Sonal A1 - Kayenaat, Aiman A1 - Songara, Dheeraj A1 - Wyllie, David J A A1 - Schuman, Erin M A1 - Kind, Peter C A1 - Chattarji, Sumantra AB -

Fragile X syndrome (FXS), a commonly inherited form of autism and intellectual disability, is associated with emotional symptoms that implicate dysfunction of the amygdala. However, current understanding of the pathogenesis of the disease is based primarily on studies in the hippocampus and neocortex, where FXS defects have been corrected by inhibiting group I metabotropic glutamate receptors (mGluRs). Here, we observe that activation, rather than inhibition, of mGluRs in the basolateral amygdala reverses impairments in a rat model of FXS. FXS rats exhibit deficient recall of auditory conditioned fear, which is accompanied by a range of in vitro and in vivo deficits in synaptic transmission and plasticity. We find presynaptic mGluR5 in the amygdala, activation of which reverses deficient synaptic transmission and plasticity, thereby restoring normal fear learning in FXS rats. This highlights the importance of modifying the prevailing mGluR-based framework for therapeutic strategies to include circuit-specific differences in FXS pathophysiology.

VL - 37 IS - 2 ER -