FMR1 and fragile X syndrome: While many of these disorders are characterized by a general down-regulation of mGluR5 and may benefit from mGluR5-positive modulators, FXS is associated with enhanced mGluR5 activity, and, indeed, various mGluR5 inhibitors can rescue cellular, electrophysiological, and behavioral defects of the Fmr1−/y mouse model of FXS.34, 35, 36, 37 The mGluR5 signaling defects that we identified in Itgb3 Het neurons are closely reminiscent of those found in the Fmr1−/y mouse model.