Significance What makes the brain tick? A simple yet challenging question that has captivated our minds for centuries. This sentiment was fittingly reflected in the launch of The BRAIN Initiative 3 years ago, spurred by the rapid advancement of noninvasive brain imaging and neuronal mapping technologies that have advanced our understanding of neural networks, which are central to brain functions and behavior. Here, we study the patterns of large-scale brain-wide interactions mediated by thalamo-cortical networks through optogenetics and functional MRI. We found that the thalamus can recruit long-range cortical and subcortical networks and initiate their interactions in a spatiotemporally specific manner. This finding provides a fresh impetus to study the mysteries of the brain.