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完成的范围，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，因此它可能是动物总体每日能量预算的主要组成部分，对体重调节具有重要意义。动物表现出的许多运动活动可能被认为是自愿的，但生物学家和心理学家不明白自愿运动如何以及为什么在野生动物物种和个体人类之间差异如此之大。先前的NSF支持被用于开发一种新的小鼠模型来研究自愿运动。超过55代的高自愿轮跑选择性育种产生了4个重复的高跑步者（HR）系，它们每天跑的距离是4个非选择对照(C)系的3倍。一个引人注目的结果是，自第16代以来，跑步表现趋于平稳，也就是说，尽管继续选择高自愿轮跑，但选择有限。这个项目源于一项显著的发现，高脂肪饮食（HFD）使HR小鼠的每日轮跑距离增加了75%，而对C小鼠几乎没有影响。在选择极限下，关于导致小鼠个体表现增加的机制的三种假设将被测试：1)HFD通过改变其独特生理成分来提高HR小鼠的耐力能力；2) HFD通过与改变后的大脑奖励系统相互作用，增加了跑轮的动机；3) HFD增加了HR小鼠的热耐受性和/或改变了热调节设定点。在这些研究之后，将对一半的品系（2 HR和2 C）进行营养环境改变，从断奶到车轮测试，同时采用标准选择方案。这项研究的这一方面将提供一个直接的测试，即喂食高脂肪饮食是否有可能使跑步表现的提高超过已经观察到的水平，这是一种跨代进化的变化，将打破选择的限制。结果将导致对自愿活动水平的全面理解，并将与脂肪动力学和肥胖、自愿运动的动机基础和活动水平的调节具有生物医学相关性。动物、组织和数据将提供给其他研究人员用于本提案未涵盖的项目。研究将强调培训研究生和本科生，包括妇女和代表性不足的群体，并将涉及与至少6个其他教员和3所其他大学的合作。与当地一名中学教师合作，将使用骨骼元素的数字研究照片来制定中学科学课程计划，旨在通过基于探究的学习，阐明科学探究与基本进化原理相结合的方法。

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.