Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 202

hypoxia and hypercapnia is during the daytime ( Fig. 8.3 ), a time when
the nocturnal rodent is less active and in a lower-energy homeostatic state,
if not sleeping 123 ; however, other time points have not been evaluated. In
rats kept in a light-dark cycle, no phase-shifting effect of acute hypoxia is
detected. 124 Encountering such powerful homeostatic stimuli during the
inactive phase should serve as a profound error signal and would alter the
timing of the clock into the active phase in which the animal is more alert
and more homeostatically and metabolically able to deal with the stimulus.
Most phase-shifting stimuli serve to move the organism from one state of
alertness to the other. For instance, when the nocturnal rodent is in its
active/dark phase and encounters light, the clock is phase shifted to the less
active state usually seen during the light phase (i.e., phase delayed when light
is encountered early in the dark period and phase advanced when encoun-
tered late in the dark period). Interestingly, both of these stimuli induce
arousal from sleep. 125-133
Just as the reason that these stimuli are able to shift the clock is not clear,
the mechanisms are also not clear. The neurotransmitters serotonin (5-HT),
neuropeptide Y, 134 pituitary adenylate cyclase activating polypeptide, 135,136
and substance P have all been shown to affect the timing of the circadian
clock when presented during the middle of the subjective daytime. Seroto-
nin can advance the timing of the peak in single-unit neuronal firing in rat
hypothalamic slices

137 and in the timing of the onset of hamster
wheel-running activity when applied into the cerebral ventricles or directly
to the SCN in vivo . 138 Serotonin neurons are robustly activated by acidosis
in vitro

in vitro

23,27,28,44-47,139-142 and by acidosis and elevations in inspired CO 2

Figure 8.3 Respiratory stimuli can modulate circadian rhythms. 24-h recordings of ham-
ster wheel-running activity on 20 consecutive days depicting the effect on the circadian
rhythms following exposure to hypoxia (A) or hypercapnia (B) as indicated. Lines are
drawn through the onset of activity for several days before stimulation and after stim-
ulation to aid in visualization of the phase shifts. Redrawn with permission from Ref. 123 .