Homeostatic response of Ppt1^−/− cortical neurons to chronic silencing is excessive upregulation of GluA1. A, Schematic of the DREADD-induced challenge paradigm and timeline (top). Representative images of DLX-hM3Dq injection in the left visual cortex (bottom right) of a WT mouse aligned to the Allen Brain atlas (bottom left). Scale bar = 50 µm for both low-magnification and high-magnification images. B, Representative immunoblot of synaptosomal GluA1 from WT, WT-DREADD, Ppt1^−/−, and Ppt1^−/−-DREADD occipital cortices and GFP-injected controls (top, all samples from same gel rearranged to match quantification) and quantification (bottom). n = 3–6 animals/group. Two-way ANOVA: interaction genotype × DREADD (F_(1,17) = 8.740, **p = 0.0088); main effect of genotype (F_(1,17) = 8.740, **p = 0.0088); main effect of DREADD (F_(1,17) = 56.65, ****p < 0.0001). Tukey's multiple comparison indicated on graph: *p = 0.0280 WT versus DREADD-WT; ****p < 0.0001 Ppt1^−/− versus DREADD-Ppt1^−/−; **p = 0.0057 DREADD-WT versus DREADD-Ppt1^−/−.