Collectively, these data demonstrate that non-ionotropic mNMDAR signaling strongly modulates the intracellular consequences of activating mGluR1/5, which have been linked to pathophysiology in several NDDs that, in addition to fragile X, include TSC,42,69SYNGAP1 haploinsufficiency,46 Rett syndrome,70 chromosome 16p11.2 microdeletion syndrome,71 and autism.72 Here, GRM1 is linked to autism.