The suprachiasmatic nucleus (SCN) in the hypothalamus is responsible for many aspects of mammalian circadian (=daily) rhythmicity. In recent studies, utilizing in vitro brain slices, we observed that the daily SCN firing profile differs between those Djungarian hamsters which exhibit photoinduction following short day exposure (e.g., gonadal regression, changes in wheel-running) and those hamsters which do not. Identification of these two different neural firing profiles in the SCN is important because it demonstrates that the SCN is a dynamic neural structure whose altered function reflects differences in overt circadian behavior (wheel-running). More important to this grant, we have discovered that two different, but stable, clock organizations (=clock structures) persist under identical environmental conditions. We can use now these unique differences in clock function to ask fundamental questions about how the neural clock is altered by different inputs. For example, how is the mammalian neural clock affected by hormonal input from melatonin (MEL). We established that MEL administration can """"""""transform"""""""" one clock state to the other, and recently we determined there is a circadian basis for MEL sensitivity in the SCN. In this research, we use both behavioral measurements and SCN slices in vitro to understand the process of MEL-induced transformation in greater detail. Two questions are addressed: 1) Is there a circadian basis for this MEL effect and is repeated MEL administration required (Experiment 1)? 2) What is the neurophysiological basis for MEL action in the SCN? That is, when, where and how does MEL act at the level of the individual SCN neuron (Experiment 2)? Given the increased interest in the possible therapeutic use of MEL in humans (e.g., jet lag, sleep disorders, and depression), it important to understand how this substance affects the basic neurobiology of clock function in the mammalian brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH052546-02
Application #
2252332
Study Section
Behavioral Neuroscience Review Committee (BNR)
Project Start
1993-09-30
Project End
1996-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Miscellaneous
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309