Small mammals and birds have a challenging lifestyle: maintaining a neutral or positive energy balance in the face of a harsh environment that is often cold and in short supply of food. A very high mass-specific metabolic rate and the inability to store a great deal of energy has led to the evolution of an extraordinary physiologica / biochemical adaptation. That physiological trait is the ability to enter torpor. When small mammals are in an energy deficit, or anticipate an energy deficit, they become torpid, a state of very low metabolic rate which allows for conservation of stored fuels for increased survival. As a consequence of the low metabolic rate, the body temperature of these small mammals declines to a large degree, as low as 20?C in mice, and lower in true hibernators. Numerous compounds, including hormones and metabolites, have been suggested as mediators of torpor. However, whether these compounds activate torpor-inducing pathways has been difficult to assess as most studies in mice examine only body temperature and/or perhaps metabolic rate, despite the complexity of the well- orchestrated physiological / biochemical / molecular changes. In this proposal, the following hypotheses will be tested: 1) all peripherally-administered compounds known to induce hypothermia and hypometabolism in mice do not resemble """"""""naturally"""""""" occurring torpor 2) adenosine administered centrally will induce a state that resembles torpor at multiple (cardiovascular, biochemical, and molecular) levels. This resubmitted proposal will employ measures that range from physiological to molecular to assess these hypotheses. These include: 1) an indirect calorimetry system, 2) a telemetry- based blood pressure / heart rate / body temperature detection system, 3) blood metabolite analysis, and 4) tissue RNA expression. One major strength of this proposal is the wide spectrum of measurements available for assessment of hypometabolic states. Williams College is a small liberal arts school that has had wonderful success excelling in both education and research endeavors. This reflects the truly supportive nature of the college towards faculty research. The administration offers an extremely beneficial sabbatical policy (every three years), built a $50 million science facility eight years ago, provides ample space for labs and animal housing, and offers intramural seed money for grant initiatives (like this one). Part of our mission in the sciences at Williams College is the exposure and successful training of undergraduates. Students regularly assume a significant amount of responsibility with research projects and the laboratory environment often takes on an atmosphere comparable to a graduate school research environment where students are working side-by-side with the faculty to design and conduct sophisticated research. My research program continues to involve undergraduates in mainstream research, exposing them to sophisticated and current technology in an integrative biology approach where testing specific hypotheses drive the research. My proposed project would provide an excellent research experience for students who are likely to go on to productive scientific careers.
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