Neuroanatomy of sleep and wakefulness

Laterodorsal tegmental and pedunculopontine tegmental (LDT/PPT) nuclei
These are situated in the dorsal pontine tegmental reticular formation and their neurones are cholinergic. They are inhibited by the locus coeruleus, raphe nuclei and tubero-mammillary nuclei. They connect to widespread areas in the brainstem and to the thalamus. They are the primary REM sleep generator [21] and when active inhibit both the locus coeruleus and the raphe nuclei. They are also involved in generation of REM sleep atonia and contribute to visual components of dreams and hallucinations.

Mesolimbic system
This arises in the midbrain ventral tegmental area and projects to the prefrontal cerebral cortex, and to the limbic system including the amygdala and hippocampus, and particularly to the thalamic reticular nucleus.

It is dopaminergic and appears to cause arousal in response to specific stimuli rather than sustained wakefulness.

Tubero-mammillary nuclei (TMN)
These nuclei are situated in the posterior hypothalamus and are histaminergic. They only receive afferent input from the ventrolateral preoptic nucleus (VLPO) and the orexin system in the lateral hypothalamus.

They inhibit particularly the VLPO and the LDT/PPT.

The TMN are most active in wakefulness, partially suppressed in NREM sleep and inactive in REM sleep. The TMN promote wakefulness and suppress both NREM and REM sleep.

Perifornical nuclei
These are located in the lateral hypothalamus and their neurones secrete orexins (hypocretins). They project to the brainstem aminergic centres, particularly the locus coeruleus, but also the raphe nuclei. They are excitatory at these sites, but lead to inhibition of the LDT/PPT. They are most active in wakefulness, which they promote, and they limit the duration of REM sleep, but have direct effect on the VLPO.

Suprachiasmatic nuclei (SCN)
The SCN are responsible for circadian rhythms and promote wakefulness. Lesions of the SCN are associated with excessive sleepiness.

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