Genetic evidence for a neurovestibular influence on the mammalian circadian pacemaker.
The mammalian circadian timing system (CTS) exerts endogenous temporal control over virtually every biochemical, physiological, and neurobiological process. Recent studies have suggested an interrelationship between the neurovestibular system, specifically the macular otoconial gravity receptors, and the CTS. To test for a functional relationship between these 2 seemingly disparate neuronal systems, the authors performed a study to evaluate the influence of the vestibular system on 3 fundamental properties of the CTS: entrainment, photic modulation, and period. The present study used a nonrecombinant mutant mouse, the head-tilt mouse (abbr. het), which lacks otoconia and hence gravity reception, to evaluate CTS function in mice lacking vestibular inputs. Circadian rhythms of body temperature (Tb) and locomotor activity (ACT) were recorded continuously by biotelemetry in het mice as well as wild-type (PWT) controls during exposure to 4 photic regimens: 12:12 LD, DD (0 micromoles s(-1) m(-2)), constant bright light (LL(B); 0.5 micromoles s(-1) m(-2)), and constant dim light (LL(D); 0.02 micromoles s(-1) m(-2)). In DD, the circadian period of the Tb and ACT rhythms was significantly longer (p < 0.001) in het than in PWT mice. In addition, the circadian period of Tb and ACT was significantly longer (p < 0.01) in LL(B) than in DD for both the het and PWT groups, although increasing ambient illuminance (i.e., DD to LL(B)) had a significantly greater (p < 0.01) period-lengthening effect in the PWT group than in the het group. The results of the present study demonstrate for the first time that the vestibular macular gravity receptors influence 2 fundamental properties of the mammalian CTS: (1) the intrinsic circadian pacemaker period and (2) the period-altering response to changes in tonic light intensity. The results of the present study thus provide the first neurobehavioral evidence for a vestibular-circadian interrelationship as well as suggest a novel mechanism underlying the signaling of activity-based nonphotic stimuli to the CTS.
Fuller
Patrick M
PM
Section of Neurobiology, Physiology & Behavior, University of California, Davis, CA 95616-8519, USA.
Fuller
Charles A
CA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D001831:Body Temperature; D002940:Circadian Rhythm / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010037:Otolithic Membrane / Q000502:physiology*; D017440:Photoperiod