Ultradian 90-min biological rhythm is attenuated in orexin-deficient mice

We recently reported that brown adipose tissue, body and brain temperature suddenly increases in an episodic manner, approximately every 90 min during the active phase of the circadian cycle in rats (Ootsuka et al., 2009, Neuroscience 164, 849–861). This ultradian rhythm correlates with tachycardia, pressor response and locomotor activity. These phase-linked ultradian episodic changes are followed by increasing of hippocampus theta-wave (5-8 Hz), a marker of cognitive processing and arousal. These observations suggest that the phase-linked ultradian episodic change in physiological variables is coordinated by central nervous system. Orexin neural system is important for arousal-sleep regulation, and thus may be related to the brain-coordinating ultradian rhythm. We test this possibility by using two types of orexin-deficient mice (orexin-knockout mice, orexin/ataxin-3 transgenic mice), and control wild-type mice. A telemetry probe (Data Science International, ETA-F10) for measurements of body temperature and ECG was implanted under 2% isoflurane anesthesia. Locomotor activity was measured by infrared beam sensors. At least one week later, a conscious unrestrained mouse was placed in an experimental cage and then all variables were measured for 36 hours under 12/12hours light-dark cycle. Ambient temperature was kept constant during the recording. Cosinor analysis was performed to compare ultradian and circadian rhythmicity between wild and orexin deficient mice. In wild-type mice, during the 12-hours active dark-period, the ultradian periodicity in locomotor activity was 86±29 min (mean±SD, n=8), and its total amplitude between 50–120 min was 14.1±7.7 (arbitrary unit). In orexin-deficient mice, the amplitude of the ultradian rhythms in locomotor activity was significantly reduced to 3.6±0.9 (P<0.01, n=8, in orexin-knockout mice), and to 7.1±4.7 (P<0.05, n=10, in orexin/ataxin-3 mice). No significant change was observed in circadian rhythmicity between orexin-deficient and wild type mice. These results support our hypothesis that orexin system contributes to the brain-coordinating ultradian rhythm.