The behavior and physiology of animals and humans are regulated by endogenously generated 24-hour (circadian) rhythms. The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that is essential for the regulation of circadian rhythms. Disruptions of circadian rhythms affect the health and well-being of millions of people and result from external disturbances such as shift-work and jet-lag and from constitutional variation of known (e.g. blindness) and unknown causes. A possible source of variation is the environment during development. The proposed project will study the development of circadian rhythms and the development of the SCN in an established animal model for circadian rhythms research, the hamster. The long-term goals of the project are: l. To understand the relationship between SCN organization and the regulation of circadian rhythms by examining this relationship during development, 2. To understand the mechanisms by which maternal physiology influences the fetal circadian pacemaker, and 3. To identify aspects of SCN development that might be subject to modification and therefore lead to long-term disruption of circadian regulation.
The Specific Aims are to test hypotheses in four critical areas: l. The role of the pineal gland hormone melatonin in the development of the mammalian circadian pacemaker, 2. The role of a specific fetal neurotransmitter system (dopamine) in the development of the circadian pacemaker; 3. The prenatal development of the SCN at the time pacemaker function begins, and 4. The postnatal development of the SCN at the time neural connections from the eyes are formed. The functional development of the pacemaker will be assessed by measuring behavioral rhythms of young hamsters and of hamsters that have received grafts of the fetal SCN. The development of the SCN will be examined with anatomical methods that include immunohistochemistry, in situ hybridization, and receptor binding assays. A unique strain of hamsters with a mutation that affects circadian rhythms will also be used. Knowledge of SCN development is essential to understand the normal as well as abnormal regulation of circadian rhythms. In addition, maternal influence on the development of fetal circadian rhythms via a dopaminergic system indicates that drugs of abuse (e.g., cocaine) can affect the development of 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 #
5R01HD018686-10
Application #
2403124
Study Section
Behavioral Neuroscience Review Committee (BNR)
Project Start
1984-04-01
Project End
1999-12-31
Budget Start
1997-05-01
Budget End
1999-12-31
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Northeastern University
Department
Biology
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