Significance The resting brain consumes enormous energy and shows highly organized spontaneous activity as often measured by functional MRI (fMRI). Using large-scale recordings from thousands of neurons, we showed a highly structured brain activity that involves the majority (∼70%) of surveyed neurons from various brain regions. It takes the form of sequential activations between two distinct neuronal ensembles and relates to low-frequency (∼0.1 Hz) modulations of arousal and hippocampal ripple activity. The finding provides a cellular-level understanding of the resting-state global brain activity often observed with fMRI and further suggests that this global activity may represent an “offline” process that links cholinergic function, memory consolidation, and perivascular clearance of brain waste.