Switches between different behavioral states of the animal are associated with prominent changes in global brain activity, between sleep and wakefulness or from inattentive to vigilant states. Arousal and attention can greatly enhance sensory processing, whereas sleep and quiet wakefulness may facilitate learning and memory. Here, I will present our recent findings on the brain circuits that are critical for regulating brain states. Cholinergic neurons in the basal forebrain (BF) promotes wakefulness and modulate cortical areas selectively. Different cell types in the BF show Noradrenergic neurons in the locus coeruleus (LC), on the other hand, show more divergent projection to the cortex. This is the first definitive proof that BF and LC projections to the cortex show both anatomical and functional differences in selectivity for modulating cortical activity