Single-neuron firing cascades underlie global spontaneous brain events

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. The resting brain consumes enormous energy and shows highly organized spontaneous activity. To investigate how this activity is manifest among single neurons, we analyzed spiking discharges of ∼10,000 isolated cells recorded from multiple cortical and subcortical regions of the mouse brain during immobile rest. We found that firing of a significant proportion (∼70%) of neurons conformed to a ubiquitous, temporally sequenced cascade of spiking that was synchronized with global events and elapsed over timescales of 5 to 10 s. Across the brain, two intermixed populations of neurons supported orthogonal cascades. The relative phases of these cascades determined, at each moment, the response magnitude evoked by an external visual stimulus. Furthermore, the spiking of individual neurons embedded in these cascades was time locked to physiological indicators of arousal, including local field potential power, pupil diameter, and hippocampal ripples. These findings demonstrate that the large-scale coordination of low-frequency spontaneous activity, which is commonly observed in brain imaging and linked to arousal, sensory processing, and memory, is underpinned by sequential, large-scale temporal cascades of neuronal spiking across the brain.