Responses to Selective Breeding for High Voluntary Activity in House Mice

运动是包括人类在内的所有动物生活的关键要素。运动能力(表现能力)设定了正常行为必须达到的限度，包括寻找食物、躲避捕食者和寻找配偶。就能量而言，运动活动可能是昂贵的，因此它可能是动物每日总能量收支的主要组成部分，对调节体重具有重要意义。动物表现出的大部分活动可能被认为是自愿的，但生物学家和心理学家不明白，为什么以及为什么自愿锻炼在野外动物物种之间或在人类个体之间存在如此大的差异。先前NSF的支持被用来开发一种新的小鼠模型，用于研究自愿运动。经过55个世代的选育，已经产生了4个重复的高奔跑者(HR)品系，它们每天的奔跑距离是4个非选择对照(C)品系的3倍。一个引人注目的结果是，从大约16代开始，跑步性能就停滞不前，也就是说，尽管继续选择高自愿性车轮跑步，但选择的范围是有限的。该项目源于一项引人注目的发现，即高脂饮食(HFD)使HR小鼠每天的车轮跑距离增加了75%，而对C小鼠几乎没有影响。我们将检验关于在选择极限下导致小鼠个体成绩提高的三个假说：1)HFD通过改变HR小鼠独特生理的组成部分提高其耐力；2)HFD通过与其改变的大脑奖励系统相互作用增加车轮跑步的动力；3)HFD增加热耐力和/或改变HR小鼠的体温调节设定点。在这些研究之后，将改变一半品系(2HR和2C)的营养环境，方法是在应用标准选择方案的同时，在断奶期间通过轮子测试给予HFD。这项研究的这一方面将直接测试喂食高脂肪饮食是否会使跑步成绩提高到超过观察到的水平，这是一种将打破选择限制的跨代进化变化。结果将导致对自愿活动水平的全面了解，并将对脂肪动力学和肥胖症、自愿锻炼的动机基础和活动水平的调节具有生物医学意义。动物、组织和数据将向其他研究人员提供，用于本提案中未涵盖的项目。研究将强调对研究生和本科生的培训，包括女性和代表性不足的群体，并将涉及与至少6名其他教师和3所其他大学的合作。与当地一名中学教师合作，骨骼元素的数字研究照片将被用来制定一份中学科学教案，旨在通过探究性学习，结合基本进化原理说明科学探究的方法。

Locomotion is a key element of the lives of all animals, including human beings. Locomotor abilities (performance capacities) set limits within which normal behaviors must be accomplished, including finding food, avoiding predators, and seeking mates. Locomotor activity can be costly in terms of energy and so it can be a major component of the overall daily energy budget of an animal, with important implications for the regulation of body weight. Much of the locomotor activity that animals exhibit may be considered voluntary, yet biologists and psychologists do not understand how and why voluntary exercise varies so widely among species of animals in the wild or among individual humans. Prior NSF support was used to develop a novel mouse model for the study of voluntary exercise. More than 55 generations of selective breeding for high voluntary wheel running have produced 4 replicate High-Runner (HR) lines that run 3-fold farther per day than 4 non-selected control (C) lines. A striking result is a plateau in running performance since about generation 16, that is, a limit to selection despite continuing to select for high voluntary wheel running. This project stems from the remarkable finding that a high-fat diet (HFD) increases daily wheel-running distances of HR mice up to 75%, with little effect on C mice. Three hypotheses about the mechanisms that cause this increase in individual performance of mice at the selection limit will be tested: 1) HFD increases endurance ability of HR mice by altering components of their unique physiology; 2) HFD increases motivation for wheel running via interaction with their altered brain reward system; 3) HFD increases thermal tolerance and/or alters the thermo-regulatory set point of HR mice. Following these studies, the nutritional environment will be altered for half of the lines (2 HR and 2 C) by administering HFD from weaning through wheel testing, while the standard selection protocol is applied. This aspect of the study will provide a direct test of whether feeding a high-fat diet will make it possible to increase running performance beyond what has been observed, a cross-generational evolutionary change that will break the selection limit. Results will lead to comprehensive understanding of voluntary activity levels and will have biomedical relevance for fat dynamics and obesity, the motivational basis of voluntary exercise, and the regulation of activity levels. Animals, tissues, and data will be made available to other researchers for projects not covered in this proposal. Research will emphasize training of graduate and undergraduate students, including women and under-represented groups, and will involve collaborations with at least 6 other faculty and 3 other universities. Working with a local middle-school teacher, digital research photographs of skeletal elements will be used to develop a middle-school science lesson plan designed to illustrate methods of scientific inquiry in conjunction with fundamental evolutionary principles through inquiry-based learning.