A highly collateralized thalamic cell type with arousal predicting activity serves as a key hub for graded state transitions in the forebrain

Sleep cycles consist of rapid alterations between arousal states including transient perturbation of sleep rhythms, microarousals and full-blown awake states. Here we demonstrate that the calretinin containing (CR+) neurons in the dorsal medial thalamus (DMT) constitute a key diencephalic node that mediates distinct levels of forebrain arousal. Cell-type-specific activation of DMT/CR+ cells could elicit active locomotion lasting for minutes, stereotyped microarousals or transient disruption of sleep rhythms depending on the parameters of the stimulation. State transitions could be induced in both slow-wave and REM sleep. The DMT/CR+ cells displayed elevated activity prior to arousal, received selective subcortical inputs and innervated several forebrain sites via highly branched axons. Together, these features enable DMT/CR+ cells to summate subcortical arousal information and effectively transfer it as a rapid, synchronous signal to several forebrain regions to modulate the level of arousal.