Fig. 2.

Deficit of histamine H₂R in mPFC glutamatergic neurons induces schizophrenia-like behaviors. (A) Schematic diagram of the site of the injected virus (Left) and representative photographs of RNAscope assays of Hrh2, CaMKIIα, and GFP mRNA (Right). (Scale bar, 20 μm.) (B1) The percentage of CaMKIIα⁺ glutamatergic neurons colabeled with GFP (Left), and the percentage of GFP⁺ cells coexpressing CaMKIIα (Right). (B2) Hrh2 expression in CaMKIIα⁺/GFP⁺ cells in CaMKIIα-Cre mice injected in the mPFC with AAV-FLEX-scramble shRNA-GFP (AAV-CON) or AAV-FLEX-shHrh2-GFP (AAV-shHrh2) to knock down H₂R. n = 3 mice. (C–H) Sensorimotor gating ability, locomotion, social behavior, hedonic function, and cognitive behavior in CaMKIIα-Cre mice injected in the mPFC with AAV-CON or AAV-shHrh2. (C) Percentage of PPI of the auditory startle reflex under 74, 78, and 82 dB prepulse intensities. (D) Distance traveled in the open field every 5 min (Left), and the total distance of AAV-shHrh2 mice traveled in the open field (Right) after administration of MK-801 and risperidone in the first 30 min. For distance moved every 5 min, n = 14 AAV-CON+Saline; AAV-CON+MK-801 and AAV-shHrh2+Saline mice, n = 13 AAV-shHrh2+MK-801 mice. For total distance of AAV-shHrh2 mice treated with risperidone and MK-801, n = 14 mice per group. (E) The nesting score (Left) and the percentage of the weight of unshredded cotton (Right) in a nest-building test. (F) Time in close interaction and preference index for a gender-matched stranger mouse (S1) and empty wire cage (E) in phase 2 and for another stranger mouse with the same gender (S2) and S1 in phase 3. (G) Sucrose preference within a 48-h period. (H) Percentage of correct alternation in the Y-maze. n = 13 for CaMKIIα-Cre+AAV-CON mice, and n = 14 for CaMKIIα-Cre+AAV-shHrh2 mice. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. See also Dataset S1 for further statistical information.