Absence of a phase-shifting response to wheel running in vestibular deficient mice
- Paper number
IAC-08.A1.1.7
- Author
Ms. Kristyn Ringgold, University of California, Davis, United States
- Coauthor
Dr. Patrick Fuller, University of California, Davis, United States
- Coauthor
Dr. Charles Fuller, University of California, Davis, United States
- Year
2008
- Abstract
The circadian timing system (CTS) generates and coordinates biological rhythms and synchronizes these physiological oscillations with the external 24-hour environment. Studies have demonstrated that the CTS is affected by changes in gravity. Therefore, to ensure crew health and performance in long-term spaceflight, alterations in CTS regulation must be understood. Studies have suggested that the CTS response to light is modified by exposure to altered gravity. However, the mammalian CTS also uses nonphotic activity-based cues, such as wheel running (WR) in rodents or exercise in humans, to coordinate the organism with its environment. Recently, our lab demonstrated a role for the neurovestibular system in the circadian responses to linear accelerations associated with changes in gravity and locomotion. These findings have led to our hypothesis that acceleration-sensing receptors in the inner ear provide the sensory flow to the CTS for the regulation of circadian phase and period by locomotor activity. To test this hypothesis, we evaluated the ability of acute WR exposure to phase shift the CTS in two groups of mice: head-tilt (het) mice (lacking macular otoconia and hence gravity reception) and wildtype (WT) littermate mice. All animals were implanted with biotelemetry transmitters for recording circadian rhythms of activity (ACT) and body temperature (Tb). After recovery all animals were released into constant darkness (DD) and assigned to wheel pulse (WP) or cage control (CC) groups. After one week, at circadian time (CT) 3, WP group mice were placed on a running wheel and those in the CC group moved to a wheel-free cage. At CT 7, all animals were moved back to their home cages, remaining in DD for 2 weeks. After re-entrainment the protocol was repeated with the WP and CC groups crossed over to the opposite condition. The magnitude of the phase shifts was calculated as the differences between ACT and Tb rhythm onset for pre- and post-wheel or cage change exposure. Four hours of wheel running produced a significant phase shift (p<.003) in rhythms in WT, but not het mice, despite equivalent wheel revolutions. The lack of a phase shift in the het group provides additional support for the concept that the vestibular macular gravity receptors provide critical afferent sensory flow to the CTS regarding changes in gravity and locomotion. These data thus provide neurobehavioral evidence for a vestibular-circadian interrelationship and a novel mechanism underlying the signaling of activity-based non-photic stimuli to the CTS. (This program was supported in part by NASA Grants NNA04CC82A and NNA07CN33G.)
- Abstract document
- Manuscript document
IAC-08.A1.1.7.pdf (🔒 authorized access only).
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