The integrated ultradian organization of behavior and physiology in mice and the contribution of orexin to the ultradian patterning

- We established a mouse model to study brain mechanisms for ultradian patterning.
- In mice, behavioral and physiological parameters increase in ultradian manner.
- Eating is integrated into the ultradian pattern.
- The integrated ultradian pattern is similar to that observed in rats.
- Orexin contributes to driving the ultradian episodic increases.

Our series of rat experiments have shown that locomotor activity, arousal level, body and brown adipose tissue temperatures, heart rate and arterial pressure increase episodically in an integrated manner approximately every 100 min (ultradian manner). Although it has been proposed that the integrated ultradian pattern is a fundamental biological rhythm across species, there are no reports of the integrated ultradian pattern in species other than rats. The aim of the present study was to establish a mouse model using simultaneous recording of locomotor activity, eating behavior, body temperature, heart rate and arousal in order to determine whether their behavior and physiology are organized in an ultradian manner in normal (wild-type) mice. We also incorporated the same recording in prepro-orexin knockout (ORX-KO) mice to reveal the role of orexin in the brain mechanisms underlying ultradian patterning. The orexin system is one of the key conductors required for coordinating autonomic functions and behaviors, and thus may contribute to ultradian patterning. In wild-type mice, locomotor activity, arousal level, body temperature and heart rate increased episodically every 93 ± 18 min (n = 8) during 24 h. Eating was integrated into the ultradian pattern, commencing 23 ± 4 min (n = 8) after the onset of an electroencephalogram (EEG) ultradian episode. The integrated ultradian pattern in wild-type mice is very similar to that observed in rats. In ORX-KO mice, the ultradian episodic changes in locomotor activity, EEG arousal indices and body temperature were significantly attenuated, but the ultradian patterning was preserved. Our findings support the view that the ultradian pattern is common across species. The present results also suggest that orexin contributes to driving ultradian episodic changes, however, this neuropeptide is not essential for the generation of the ultradian pattern.