Resting state fMRI shows increased global synchrony in schizophrenia at rest, but mechanisms remain speculative. We tested mice with knockout of SynCAM1 (related to synaptic organization), LRRTM1 (related to schizophrenia symptoms) and both genes using whisker-stimulation and resting-state fMRI. SynCAM1 was linked to stronger whisker barrel activation and to greater functional connectivity. However, this was lost if global signal regression was performed. Global signal amplitude was significantly higher in SynCAM1 knockout mice, and amplified by the additional knockout of LRRTM1. We hypothesize this is due to disrupted synaptic connections by SynCAM1 knockout, which are partially protected when LRRTM1 is present.