Thalamic dual control of sleep and wakefulness

Slow-waves (0.5 - 4 Hz) predominate in the cortical electroencephalogram during non-rapid eye movement (NREM) sleep in mammals. They reflect the synchronization of large neuronal ensembles alternating between active (UP) and quiescent (Down) states and propagating along the neocortex. The thalamic contribution to cortical UP-states and sleep modulation remains unclear. Here we show that spontaneous firing of centromedial thalamus (CMT) neurons in mice is phase advanced to global cortical UP-states and NREM–wake transitions. Tonic optogenetic activation of CMT neurons induces NREM–wake transitions, whereas burst activation mimics UP-states in the cingulate cortex (CING) and enhances brain-wide synchrony of cortical slow-waves during sleep, through a relay in the antero-dorsal thalamus (AD). Finally, we demonstrate that CMT and AD relay neurons promote sleep recovery. These findings suggest that the firing pattern of CMT neurons can modulate brain-wide cortical activity during sleep and provides dual control of sleep-wake states.