In mammals, the circadian system influences many physiologic processes. During development, the circadian system may influence neonatal growth and behavior, and may play a role in the pathogenesis of illnesses including Sudden Infant Death Syndrome. In contrast to what is known in rodents, little is known about the development and function of the circadian timing system in primates. This application represents a focused effort using physiological, molecular and biochemical approaches to characterize the development of the circadian system in a primate. The hypothalamic suprachiasmatic nuclei (SCN) are the site of a biological clock generating and regulating numerous circadian rhythms. In placental mammals, the SCN begin oscillating in utero. Before the SCN are innervated by the retina, the mother regulates (entrains) the oscillations of the fetal clock. Some time after innervation of the SCN by the retina, the light-dark cycle regulates clock activity. For several reasons, it is not feasible to use humans or other non- primate species for these proposed developmental studies. Baboons (Papio species) are excellent models of human development, and as such, will be used in the proposed experiments. First, using histologic and receptor localization methods, we will examine the anatomical development of the SCN. Second, using the [14C]-deoxyglucose method, we will determine when the fetal SCN begin to oscillate. Third, we will characterize the development of physical and humoral circadian rhythms in term and preterm animals. Fourth, we will use biochemical methods to determine the onset of photic responsiveness and examine molecular responses to light in the SCN. Fifth, we will examine how light regulates the timing of the developing clock. Many physiologic activities and pathologic processes are synchronized with the daily light-dark cycle. Understanding the development of circadian rhythmicity in primates will better allow us to understand neonatal physiology and environmental influences on the developing infant.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology B Subcommittee 2 (NEUB)
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Kitt, Cheryl A
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Yale University
Schools of Medicine
New Haven
United States
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Rivkees, Scott A (2007) The Development of Circadian Rhythms: From Animals To Humans. Sleep Med Clin 2:331-341
Rivkees, Scott A (2004) Emergence and influences of circadian rhythmicity in infants. Clin Perinatol 31:217-28, v-vi
Rivkees, Scott A; Mayes, Linda; Jacobs, Harris et al. (2004) Rest-activity patterns of premature infants are regulated by cycled lighting. Pediatrics 113:833-9
Rivkees, Scott A (2003) Rest-activity patterns in children with hypopituitarism. Pediatrics 111:e720-4
Rivkees, Scott A (2003) Developing circadian rhythmicity in infants. Pediatr Endocrinol Rev 1:38-45
Rivkees, Scott A (2003) Developing circadian rhythmicity in infants. Pediatrics 112:373-81
Rivkees, S A (2001) Mechanisms and clinical significance of circadian rhythms in children. Curr Opin Pediatr 13:352-7
Rivkees, S A (2001) Arrhythmicity in a child with septo-optic dysplasia and establishment of sleep-wake cyclicity with melatonin. J Pediatr 139:463-5
Hao, H; Rivkees, S (2000) Melatonin does not shift circadian phase in baboons. J Clin Endocrinol Metab 85:3618-22
Rivkees, S A; Hao, H (2000) Developing circadian rhythmicity. Semin Perinatol 24:232-42

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