Advisor(s)

Frederick Charles Davis

Contributor(s)

Joseph Ayers, Erin J. Cram, Jeanne F. Duffy, Donald M. O'Malley

Date of Award

2010

Date Accepted

12-2010

Degree Grantor

Northeastern University

Degree Level

Ph.D.

Degree Name

Doctor of Philosophy

Department or Academic Unit

College of Arts and Sciences. Department of Biology.

Keywords

animal physiology, amygdala, circadian, fear, Per2, prokineticin, VIP

Subject Categories

Mammals - Physiology, Circadian rhythms

Disciplines

Biology, general | Other Animal Sciences

Abstract

It is well known that the suprachiasmatic nucleus (SCN) is the master clock in mammals, however, how the SCN signals to other brain areas to regulate circadian rhythms is not yet known. The first two chapters in this thesis explore potential SCN output signals that may serve to entrain slave oscillators in other brain regions and other organs. Infusion of agonists or antagonists for the VIP receptor, as well as prokineticin 2, into the third ventricle of hamsters identified the role of VIP signaling in regulating light effects on the SCN in comparison to the role of prokineticin 2 as an SCN output signal that inhibits activity.

Clock genes regulate the circadian rhythms of cells in the master clock of mammals, the SCN, but the functions of clock genes in tissues outside of the SCN has not yet been determined, although some evidence indicates that they are involved in coordinating the daily tasks of the specific tissues in which they are expressed. The third chapter explores how a biologically relevant stimulus, entrainment to a fearful odor, can affect the circadian rhythm of clock proteins in brain regions responsible for processing the fearful stimulus, the amygdala, pririform cortex, and hippocampus, as well as inhibit activity of the animals separately from the SCN. This experiment provides evidence that the amygdala, piriform cortex, and hippocampus can potentially function as oscillators separately from the SCN to coordinate entrainment to a fearful stimulus.

Rhythms in the SCN exist since birth, but the age during which rhythms in peripheral brain regions develop is not known. Identifying this age may provide insight into how the SCN regulates rhythms in these areas, and possibly a potential critical period of development of rhythms in other brain areas. We examined the development of rhythms in Per2 expression in the amygdala, hippocampus, and piriform cortex. Rhythms in all of these areas were not present at P15, and where antiphase to rhythms in adult animals at P20. Adult rhythms did not appear until P30.

Taken together, these results indicate that VIP transmits light information to SCN cells, and modulates the length of circadian period and phase advances in response to light stimulation. The SCN in turn regulates circadian rhythms in activity through prokineticin 2, and likely other output signals. Rhythms in other brain regions such as the amygdala, piriform cortex, and hippocampus however can uncouple from the SCN when entrained to other biologically relevant stimuli such as a fearful odor. Normal adult rhythms in these regions however do not develop until P30, indicating that SCN output signals regulating these rhythms are not fully developed until late postnatal ages.

Document Type

Dissertation

Rights Holder

Harry Pantazopoulos


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