β1-integrins in the OFC are necessary for sensitivity to cortical inputs. A, Experimental design. Mice were infused unilaterally with control viral vectors or hM4Di-DREADD in the PL and control viral vectors or CaMKII-driven Cre in the OFC, also referred to as the “oPFC”. Hemispheres were counterbalanced. When infusions were ipsilateral, one intrahemispheric PL→OFC interaction was unaffected. When infusions were contralateral, both intrahemispheric PL→OFC connections were affected, represented by red crosses. If β1-integrins in the OFC sustain sensitivity to intrahemispheric PL inputs, then contralateral infusions will occlude behavioral response updating. The arrows on the control condition indicate that the control group contained ipsilateral and contralateral control viral vectors. B, Histological representation of PL infusions, with black representing the largest infusion and white the smallest on coronal sections from the Mouse Brain Library (Rosen et al., 2000). C, Timeline of experimental events, including the administration of the DREADD ligand CNO to all mice, regardless of viral vector expression, 1 h before access to water (baseline) or sucrose. D, With repeated access to a palatable 1% w/v sucrose solution, intake in control mice increases, presumably as mice develop a sucrose expectation. Intake in mice with contralateral infusions was blunted, suggesting that β1-integrins are necessary for OFC sensitivity to intrahemispheric PL inputs that help to develop and sustain expectations. Mice with ipsilateral infusions differed from neither control nor contralateral groups, an apparent intermediate phenotype (n = 8 control, n = 9 ipsilateral, n = 10 contralateral). Data are shown as mean + SEM. *p < 0.05 versus control, @p < 0.05 control mice on the first versus last sucrose day. Cg1, Cingulate cortex, PL=prelimbic cortex, mOFC, medial OFC. This experiment was conducted twice with concordant outcomes; due to baseline consumption differences, one cohort is represented here.