Natural environments vary considerably over the course of every 24-hour cycle and organisms have evolved mechanisms to adapt to these temporal changes, including endogenous oscillators that generate rhythms having a period of approximately one day (i.e., circadian oscillators or clocks). In mammals circadian rhythms in physiology and behavior are controlled to a large extent by a circadian clock located in a region of the brain called the suprachiasmatic nucleus (SCN), but there are secondary circadian oscillators in other brain regions, as well as in many organs outside the brain. The primary goal of our research program is to elucidate how different components of this multi-oscillator system differ between diurnal mammals and the nocturnal species that traditionally have been used in mechanistic experimentation in circadian biology. We will do this using a diurnal rodent model, the Nile grass rat. Work with this model has served to identify many similarities between nocturnal and diurnal animals in the functioning of the SCN, but also has served to identify remarkable differences in the functioning of a region just dorsal to it, known as the lower- subparaventricular zone (LSPV), where an extra-SCN circadian oscillator resides in the diurnal grass rat. Our approach will first evaluate the functional anatomy of the LSPV and the role it plays in the control of rhythms and secondary oscillators in the brain and in internal organs. Second, we will evaluate how the coupling between the molecular clock of the SCN and secondary oscillators in and outside the brain differs between diurnal grass rats and nocturnal laboratory rats. Third, we will determine how the coordination of molecular rhythms in various regions of the brain and body is altered when a diurnal mammal makes a spontaneous shift in its temporal distribution of activity and becomes primarily night active. Our work has important implications for human mental and physical health because most mechanistic biomedical research on circadian rhythms is done using nocturnal rodent models, yet somewhere in the brains of these animals basic timekeeping functions differ dramatically from those operating in diurnal species like us. Only by understanding these differences can we begin to identify which principles and patterns that emerge from research with nocturnal mammals apply to humans and which do not. In addition, our work with diurnal animals that spontaneously become active at night will reveal how rhythms in various regions of the brain and body can become damped or desynchronized under conditions like those human endure during shift work. These insights will help us understand and eventually alleviate the myriad medical and behavioral problems faced by shift workers, who represent 16% of Americans
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