Circadian rhythms are oscillations of behavior and physiology with a period of approximately 24 hours that are generated by an endogenous biological timing mechanism, that is, a biological clock. In mammals the master circadian clock is located within the suprachiasmatic nucleus of the hypothalamus (SCN). The SCN is composed of thousands of single cell circadian oscillators (neurons) that together produce a rhythmic output that sets the time for a diversity of rhythms like hormonal release cycles, sleep and wakefulness, and body temperature rhythms. We have recently shown that the SCN of rats exposed to artificially short days (22 h) can be dissociated into two subregions, the SCN core and shell, that oscillate independently and that are associated with two rhythms of locomotor activity, one with a period of 22 hours and the other with the rat endogenous period of 24.9 hours.
Specific Aim A.1 proposes experiments to determine whether this animal model presents features of human forced desynchronization and may therefore represent a good animal model for human internal desynchronization. Experiments in Specific Aim A.2 exploit the rat forced desynchronization model to identify output pathways by which the SCN regulates endocrine rhythms that are likely to rely differentially on the circadian activity of the SCN core or that of the SCN shell.
For Specific Aim A.3 we propose to develop an in vitro model of the forced desynchronized rat SCN to study the coupling mechanisms between the SCN core and shell. The experiments proposed in this application will unmask specific output pathways by which the master circadian oscillator of mammals times specific rhythmic outputs. Furthermore, the experiments will establish the foundations for the potential use of the forced desynchronized rat model to study the neural bases of human internal synchronization and intercellular coupling in the SCN.
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