Recent evidence indicates a putative mouse homologue of the human triple-network model, for which a salience network (SN) actively engages either internally-oriented default mode network (DMN) or externally-oriented central executive network (CEN). The interaction amongst these homologues has yet to be validated. This study probed SN responses to DMN inhibition in mice, during functional magnetic resonance imaging. We found that SN radically adjusts its connectivity profile with triple-network components, depending on which DMN hub is inhibited. This indicates that triple-network must be considered holistically, with SN serving an important role in overall triple-network connectivity.