Physiological homeostatic regulatory systems mature in parallel early in life. Of particular relevance to Sudden Infant Death Syndrome (SIDS) are the systems controlling sleep and arousal, circadian rhythms, body temperature, and breathing. Profound interactions between these regulatory systems occur in adults; however, little is known about the developmental aspects of these interactions. The premise of this research program is that the nature of the interactions between these regulatory systems shows marked changes during early development, and the etiology of SIDS may reside in those changes. Our goals are therefore (1) to bring together in one animal model complementary studies of the development of circadian control, sleep architecture and homeostasis, thermoregulation, and respiratory control, (2) to characterize systems interactions at different developmental stages, and (3) to compare animal model research with parallel studies from human infants. One basic hypothesis these research projects will investigate is that various factors can converge to favor prolonged REM sleep bouts and/or to decrease arousal, which could increase SIDS risk. The first of the four research components will characterize the development of sleep homeostasis and biological clock dependent arousal in the rat, using an unprecedented sleep bioassay facility and resource ("SCORE"). This technology, which allows state-of-the-art assessment of sleep-wake stages, sleep organization, and analysis of the relationship between sleep and other physiological systems, is a central core resource for this entire program. The second research component addresses the mechanisms underlying the association of temperature with SIDS by investigating environmental and body temperature influences on sleep distribution, arousal, and control of breathing, and the combined effects of temperature and sleep deprivation on sleep architecture and arousal. The hypotheses central to the third research component are that perturbations of the circadian system, or delayed maturation of the circadian system, are contributory factors to SIDS via the strong ties between the circadian system and the control of sleep and arousal. The studies in this research component will provide basic information on the development of the circadian system in both the rat and human infant. The final research component will examine the interaction of temperature with sleep and respiration in human infants at several stages of development, allowing a unique opportunity to provide a parallel clinical complement to the studies proposed in the animal model. Stanford University is ideally situated for the creation of a Perinatal Emphasis Research Center (PERC) with a focus of sleep, biological rhythms, physiological homeostasis, and SIDS. The integrated, multidisciplinary research approach to be utilized at this PERC will facilitate and formalize the interactions of these various units, and bring considerable expertise and technologies to bear on exploring both animal model and human infant studies investigating the development of physiological regulatory systems believed to play critical roles in SIDS.