Brain-Wide Spatiotemporally Distinct Traveling Waves Drive Anxiety-Like Behaviors in Mice

Cortical traveling waves coordinate communication among distributed neural ensembles to modulate brain function and dysfunction through distinct spatiotemporal propagation patterns. However, the brain-wide propagation dynamics of traveling waves from different origins and their roles in regulating behavior remain unclear. Using optogenetics alongside whole-brain fMRI in mice, it is demonstrated that optogenetic activation of the medial prefrontal cortex and primary somatosensory area induces cortical spreading depression (CSD)-like traveling waves. These waves propagate beyond the ipsilateral cortex to the contralateral cortex and midbrain, reaching subcortical structures along cortico-amygdala-striatal pathways, ultimately terminating in the striatum ≈4 min after induction. The propagation directions in the cortex, speed, duration, and region involvement vary with wave origins. Furthermore, these CSD-like traveling waves induce anxiety-like behaviors and increase dendritic spine density. The findings elucidate the complete process from induction to termination of traveling waves across the whole brain and reveal their previously undiscovered role in driving anxiety.