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mise à jour 8
août 2002
Nature Reviews
Neuroscience
2002;3(8):591-605
The
neurobiology of sleep: genetics, cellular
physiology and subcortical
networks
Abstract : To
appreciate the neural underpinnings of sleep,
it is important to view this universal
mammalian behaviour at multiple levels of its
biological organization. Molecularly, the
circadian rhythm of sleep involves
interlocking positive- and negative-feedback
mechanisms of circadian genes and their
protein products in cells of the
suprachiasmatic nucleus that are entrained to
ambient conditions by light. Circadian
information is integrated with information on
homeostatic sleep need in nuclei of the
anterior hypothalamus. These nuclei interact
with arousal systems in the posterior
hypothalamus, basal forebrain and brainstem
to control sleep onset. During sleep, an
ultradian oscillator in the mesopontine
junction controls the regular alternation of
rapid eye movement (REM) and non-REM sleep.
Sleep cycles are accompanied by
neuromodulatory influences on forebrain
structures that influence behaviour,
consciousness and cognition.
[...]
Conclusions
Over the past decade,
a remarkable explosion of new findings has
allowed us to construct a much more complete
picture of the genetic mechanisms, cellular
neurophysiology and subcortical networks that
underlie the neurobiology of sleep. This
explosion has been made possible by
technological advances in molecular biology
and biotechnology (such as gene cloning and
DNA sequencing), as well as in cellular
neurophysiology (such as sophisticated
combinations of microdialysis, unit
recording, axonal tracers and
immunohistochemistry). We now know that an
interlocking positive - negative feedback
mechanism that controls gene transcription in
individual cells of the SCN of the
hypothalamus is the molecular basis of
circadian rhythmicity in mammals. This
endogenous periodicity can be entrained to
the ambient photoperiod by photons that
impinge on the circadian
photopigment,melanopsin, in RGCs, which
convey this information to the SCN
monosynaptically through the RHT. Circadian
rhythmicity emerges from SCN cells by action
potentials that impinge on adjacent nuclei of
the anterior hypothalamus, including the PVH,
SPZ and DMH; in turn, these nuclei convey
circadian rhythmicity to structures that
control rhythmic physiological processes,
such as sleep, temperature and endocrine
output. Feedback to the SCN circadian
oscillator can occur through melatonin from
the pineal gland, which reliably secretes
this sleep-related hormone in response to
polysynaptically conveyed signals from the
SCN. A key hypothalamic structure that
receives circadian output from the SCN
through the SPZ and the DMH is the VLPO,
which promotes NREM sleep. The VLPO might
initiate sleep onset through reciprocal
inhibition of cholinergic, noradrenergic and
serotonergic arousal systems in the
brainstem, as well as histaminergic systems
of the posterior hypothalamus and cholinergic
systems of the basal forebrain, all of which
are modulated by the orexinergic arousal
system of the lateral hypothalamus. These
arousal systems conspire to promote the
activated brain states of waking,whereas the
cholinergic system acts alone to promote the
activated state of REM sleep.
