Understanding how macroscale brain dynamics are shaped by microscale mechanisms is crucial in neuroscience. We investigate this relationship in animal models by directly manipulating cellular properties and measuring whole-brain responses using resting-state fMRI. Specifically, we explore the impact of chemogenetically neuromodulating D1 medium spiny neurons in the dorsomedial caudate putamen (CPdm) on BOLD dynamics within a striato-thalamo-cortical circuit in mice. Our findings indicate that CPdm neuromodulation alters BOLD dynamics in thalamic subregions projecting to the dorsomedial striatum, influencing both local and inter-regional connectivity in cortical areas. This study contributes to understanding structure–function relationships in shaping inter-regional communication between subcortical and cortical levels.