Distinct spiking sequences mediate global brain state transitions

Brain undergoes function-related global states transitions, but their neural mechanisms remain unclear. Using brain-wide single-unit recordings from 46,496 mouse neurons, we investigated transitions between non-rapid eye movement (NREM) sleep and wakefulness at high spatiotemporal resolution. These transitions were accompanied by direction-selective transient spike sequences across distinct brain regions. Optogenetic inhibition of medial dorsal thalamus, activated at wake-to-NREM sequence onset, selectively blocked wake-to-NREM transition without affecting reverse transition or state maintenance. Recurrent neural networks trained on state-switching tasks similarly relied on sequential activities for state transitions. These dynamics followed direction-selective slow manifolds linking discrete attractors, which are not predicted by existing theories. Together, we identified previously unknown transient spike sequences governing global brain state transitions and the necessity of a brain region in gating this process.