This project will examine the entrainment of circadian rhythms during early mammalian development. An critical feature of circadian regulation is the interaction of circadian oscillators with environmental cycles (entrainment) or with other circadian oscillators within the individuals organism. Such interactions establish specific, functionally important phase relationships among rhythms(temporal organization). A central hypothesis underlying research on human circadian rhythms is that the maintenance of temporal organization is important for human health. How circadian oscillators interact to maintain temporal organization is not understood. A unique opportunity to address this problem comes from a striking case of temporal organization that occurs during mammalian development; a circadian pacemaker in the offspring becomes entrained by the circadian pacemaker of the mother. Because the entrainment begins prenatally, this case of temporal organization provides a unique model in which the interactions between distinct and identified circadian pacemakers within the same physiological system(the mother) can be studied. The project will study the temporal relationship between the behavioral rhythms of the mother and her pups in the Syrian hamster(Mesocricetus auratur). Activity rhythms can be rigorously quantified only 35 days after fertilization and can be used to measure the relationships established by entrainment at an earlier age. Entrainment at early ages will also be directly tested by transplanting fetal tissue to an adult host and measuring the restored behavioral rhythms. Goals of the project are to identify the signals that mediate entrainment and to determine if there is a critical stage in pacemaker development when entrainment occurs. Of particular interest is the role of the pineal gland hormone, melatonin. Melatonin has already been implicated as an entraining signal and melatonin might have therapeutic applications for disorders related to circadian rhythms.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018686-06
Application #
3315797
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1984-04-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1993-06-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Northeastern University
Department
Type
Schools of Arts and Sciences
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02115
Lorelli, Christina J; Wreschnig, Daniel; Davis, Fred C (2011) Resilience of circadian pacemaker development in hamsters. J Biol Rhythms 26:221-9
Kabrita, Colette S; Davis, Fred C (2008) Development of the mouse suprachiasmatic nucleus: determination of time of cell origin and spatial arrangements within the nucleus. Brain Res 1195:20-7
Viswanathan, N; Davis, F C (1993) The fetal circadian pacemaker is not involved in the timing of birth in hamsters. Biol Reprod 48:530-7