Control of sleep and wakefulness by brainstem monoaminergic and cholinergic neurons

Noradrenergic projection originating in the locus coeruleus, serotonergic projection from the dorsal raphe nucleus, and cholinergic projection from neurons gathering in the laterodorsal tegmental nucleus and scattering in the pedunculopontine tegmental nucleus constitute three diffuse projection systems arising from the brainstem and innervating wide areas of the brain. They may function as controllers of sleep and wakefulness. We have investigated functional roles of the projections by recording neuronal activity in these brainstem nuclei, and by observing effects of stimulation of the brainstem nuclei. The projection from the locus coeruleus is an arousal system, since the noradrenergic neurons are active specifically during waking, and activation of the noradrenergic projection excites upper brain structures. Functions of the serotonergic projection are still mysterious, since its action on upper brain is inhibitory in spite of waking-specific activity of the neurons. A group of cholinergic neurons constitute a system to induce and maintain paradoxical sleep. The cholinergic projection may have another role, i.e. to induce a rapid, transient elevation of vigilance level by their phasic response to novel, unfamiliar stimuli.