Fig 1A. mGluR5 activation increases coupling of the receptor specifically with Gq/11 in the DLPFC. Synaptic membranes derived from DLPFC tissues were preincubated with 0.5 nM [35S]GTPɤS for 5 min and with or without 10 µM of mGluR5 antagonist, ACDPP. The reaction was further incubated with or without 0.1 or 1 µM of CHPG for 10 min. [35S]GTPγS binding to Gα was captured by IP for specific Gα subunit. N = 4. Fig 1B. CHPG induced downstream signaling is reduced in the DLPFC of patients compared to controls. Postmortem DLPFC slices were analyzed for CHPG induced activation of mGluR5 signaling using the postmortem receptor activation paradigm. Tissue slices from 17 matched pairs of patients and controls were incubated with 0, 0.1, 1 μM CHPG, synaptic membranes were IPed for mGluR5 and Gq/11 coupling, activation of PI3K and association with Homer were assessed. Striking alterations in all three parameters in the patient group.