Neurovestibular modulation of circadian and homeostatic regulation: Vestibulohypothalamic connection?

Abstract

Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (T(b)), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in T(b) and an attenuated T(b) circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice (P < 0.0001). In contrast, the het mice did not exhibit a decrease in mean T(b) and only a slight decrease in T(b) circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

Entrainment of the human circadian pacemaker to longer-than-24-h days

“…In these situations, sleep and circadian disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews (46,47). Moreover, long-duration exploration class space missions may require astronauts to be scheduled to non-24-h light:dark periods for extended durations of time in conditions in which gravity could additionally impact circadian physiology (48). The above issues highlight the importance of developing effective countermeasures to maintain circadian entrainment.…”

Sleep and Circadian Rhythms in Humans

“…This is reflected by our performance on the single most safety-sensitive task that is shared in common by most American adults: driving motor vehicles on the nation's highways. This routine highly over-learned task performed in a moving vehicle, the motion of which stimulates the neurovestibular input to the ventrolateral preoptic (VLPO) area (Fuller et al 2002), provides a setting that can unmask elevated homeostatic sleep drive. Sleep loss and misalignment of circadian phase increase the likelihood that the VLPO area of the hypothalamus will initiate an involuntary transition from wakefulness to sleep (Saper et al 2005).…”

Vestibular loss disrupts daily rhythm in rats

“…The vestibular system is primarily involved in gaze stabilization and postural control (23), but its influence has been expanded to autonomic and bone regulation (11,61,63), spatial learning and memory (5, 6, 56), and spatial orientation and perception of gravitational verticality (37). Studies carried out in environments in which gravity is altered have shown evidence of a possible influence of the vestibular system on hypothalamic circadian function in rats (27) and mice (18,46 …”

“…The vestibular system is primarily involved in gaze stabilization and postural control (23), but its influence has been expanded to autonomic and bone regulation (11,61,63), spatial learning and memory (5,6,56), and spatial orientation and perception of gravitational verticality (37). Studies carried out in environments in which gravity is altered have shown evidence of a possible influence of the vestibular system on hypothalamic circadian function in rats (27) and mice (18,46); disruption of circadian rhythms of temperature (Temp) and locomotor activity (Act) have been similarly observed in both species for about 7 days in a 2 G environment generated by a centrifuge. Knockout mice devoid of otolithic vestibular sensors [het(Ϫ/Ϫ) mice] remained unaffected by hypergravity at 2 G (18).…”

“…Studies carried out in environments in which gravity is altered have shown evidence of a possible influence of the vestibular system on hypothalamic circadian function in rats (27) and mice (18,46); disruption of circadian rhythms of temperature (Temp) and locomotor activity (Act) have been similarly observed in both species for about 7 days in a 2 G environment generated by a centrifuge. Knockout mice devoid of otolithic vestibular sensors [het(Ϫ/Ϫ) mice] remained unaffected by hypergravity at 2 G (18). However, when placed in constant darkness (DD) or bright light conditions (LL), they showed an altered period-lengthening response compared with wild-type mice (the latter exhibiting a free-running activity rhythm) (16a).…”