Neurochemical aspects of sleep regulation with specific focus on slow-wave sleep

Abstract

The purpose of this review is to outline the mechanisms responsible for the succession of the three vigilance states, namely waking, non rapid eye movement (nonREM) and REM (paradoxical) sleep over 24 h. The latest hypothesis on the mechanisms by which cortical activity switches from an activated state during waking to a synchronised state during nonREM sleep is presented. It is proposed that the activated cortical state during waking is induced by the activity of multiple waking systems, including the serotonergic, noradrenergic, cholinergic and hypocretin systems located at different subcortical levels. In contrast, the neurons inducing nonREM sleep are all localized in a single small nucleus named the ventrolateral preoptic nucleus (VLPO) situated above the optic chiasm. These neurons all contain the inhibitory neurotransmitter γ-aminobutyric acid. The notion that the switch from waking to nonREM sleep is due to the inhibition of the waking systems by the VLPO sleep-active neurons is introduced. At the onset of sleep, the sleep neurons are activated by the circadian clock localized in the suprachiasmatic nucleus and a hypnogenic factor, adenosine, which progressively accumulates in the brain during waking.

Key words::

• Waking systems
• sleep mechanisms
• nonREM sleep
• REM sleep
• slow-wave sleep

Acknowledgements

This work was supported by Centre National de la Recherche Scientifique, Université de Lyon and Université Lyon 1. Medical writing assistance for the preparation of this manuscript was provided by Wolters Kluwer Medical Communications. This assistance was funded by sanofi-aventis.

Statement of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.