Thalamus mediates neocortical Down state transition via GABA_B-receptor-targeting interneurons

Slow-wave sleep is characterized by near-synchronous alternation of active Up states and quiescent Down states in the neocortex. Although the cortex itself can maintain these oscillations, the full expression of Up-Down states requires intact thalamocortical circuits. Sensory thalamic input can drive the cortex into an Up state. Here we show that midline thalamic neurons terminate Up states synchronously across cortical areas. Combining local field potential, single-unit, and patch-clamp recordings in conjunction with optogenetic stimulation and silencing in mice in vivo, we report that thalamic input mediates Down transition via activation of layer 1 neurogliaform inhibitory neurons acting on GABA_B receptors. These results strengthen the evidence that thalamocortical interactions are essential for the full expression of slow-wave sleep, show that Down transition is an active process mediated by cortical GABA_B receptors, and demonstrate that thalamus synchronizes Down transitions across cortical areas during natural slow-wave sleep.