Control of Sleep and Wakefulness in Health and Disease - Progress in Molecular Biology and Translational Science - page 147

Close to the VLPO are a distributed group of neurons in the hypotha-
lamic preoptic area that increase firing in response to warming (so-called
warm-sensitive neurons or WSNs). 68 WSNs are preferentially active during
sleep, and they exhibit an increase in firing in anticipation of the transition
from wake to sleep. 69 Activation of these neurons leads to inhibition of
wake-promoting neurons in the lateral hypothalamus and basal forebrain
and a subsequent increase in NREMS. 70 Unlike the VLPO, however, these
neurons do not appear to have direct, reciprocal innervation from wake-
promoting areas of the brain and are, therefore, likely involved in the mod-
ulation but not stability of the sleep state. These WSN are also likely not
involved in the circadian- and sleep-modulation of body temperature 71
or changes in sleep in response to fever, 72 but may be involved in modulat-
ing sleep in response to changes in environmental temperatures.
Robust changes in temperature often accompany immune responses,
which are themselves linked to changes in sleep. Molecules nominally linked
to the immune system, such as the cytokines interleukin-1 b (IL1 b ) and
tumor necrosis factor- a (TNF a ), may also play a role under non-
pathophysiologic conditions. When given exogenously at nonpyrogenic
concentrations, both IL1 b and TNF a can increase NREMs. 73 When ani-
mals are sleep deprived, both of these cytokines increase in concentration
in the cerebrospinal fluid. 74 These and other data have led to the suggestion
that levels of IL1 b and TNF a may act as a downstream signal of a homeo-
static drive for sleep, possible being a stable, biochemical expression of
extracellular ATP concentrations. 75 IL1 b and TNF a might mediate their
hypnogenic effect through activation of sleep-promoting neurons in the
preoptic area and inhibition of wake-promoting neurons in the
hypothalamus, 76 though their effects may be more widespread. Under con-
ditions of infection, there is a further, immune-stimulated increase of IL1 b
and TNF a . This may be responsible for the commonly observed increase in
sleep during many active and some chronic infections.
3. THE CORTEX
Most of this chapter has discussed the fairly well-characterized effects
of subcortical structures on sleep and wake. Vis-`-vis the cortex, these struc-
tures can be simply described as coordinating the movement of cortical neu-
rons into “wake” and “sleep” states. There is growing evidence that cortical
neurons may exhibit “local” patterns of sleep. One of the first examples in
the human literature of sleep occurring at a local level was the demonstration