Responses to Artificial Selection for Voluntary Activity in Mice

自然选择和性选择作用于复杂的、高度整合的表型，但进化反应如何在生物组织的多个层次上发生的理论并不全面，现有的经验检验既零碎又不确定。以前的NSF支持允许开发一个新的模型系统来研究高运动活动选择的多层次进化反应。用远交实验小鼠进行了高自愿跑轮的选择性繁育。到第16代，4个重复选择(S)系的小鼠比4个随机对照(C)系的小鼠多跑170%（雌性，“15对5.5公里/天”）。这种差异持续到17-29代，表明存在选择限制。活动的增加主要是由于跑步速度的提高。美国小鼠在断奶和至少18个月时跑得更多。拟议的研究将测试生理限制选择的本质，阐明运动适应的机制，并探索活动增加的神经生物学。研究将重点培养研究生和本科生，以及博士后研究人员。据推测，最大有氧速度的进化可塑性的缺乏限制了轮式跑的进一步增加。增加和减少氧气对车轮运行和最大耗氧量的影响将被研究。运动的能量消耗将在轮式和跑步机上进行测量。肺弥漫性将以形态计量学估计。骨骼的组成部分将检查大小，形状，对称性和二次重塑的数量的差异。肌球蛋白重链异构体的表达将在后肢肌肉中被量化，而“强大的微型肌肉”出现在两个选定的细胞系中，将被生化和电子显微镜表征。对于上述许多性状，遗传和表型可塑性以及潜在的相互作用，将通过测量长期饲养或不饲养的S和C小鼠来检验。以cFos作为神经元活动指标的免疫细胞化学将用于比较S和C小鼠在休息和高峰跑轮时的关键大脑区域（动机、奖励、成瘾、运动自主控制、空间记忆和学习）。结果将导致一个全面的了解如何增加的活动水平演变在一个模式哺乳动物系统。老鼠将提供给其他研究人员，它们将成为研究运动对身体健康和衰老影响的重要模型。

Natural and sexual selection act on complex, highly integrated phenotypes, but theories of how evolutionary response will occur across multiple levels of biological organization are non-comprehensive, and existing empirical tests are both fragmentary and inconclusive. Previous NSF support allowed development of a novel model system to study multi-level evolutionary responses to selection for high locomotor activity. Selective breeding for high voluntary wheel running was implemented with outbred laboratory mice. By generation 16, mice in the 4 replicate selection (S) lines ran 170% more than in the 4 randombred control (C) lines (for females, " 15 vs. 5.5 km/day). This difference continued for generations 17-29, indicating a selection limit. Increased activity has occurred primarily by higher running speed. S mice run more at weaning and for at least 18 months. Proposed research will test the nature of the physiological limit to selection, elucidate the mechanisms of locomotor adaptation, and explore the neurobiology of increased activity. Research will emphasize training of graduate and undergraduate students, as well as a postdoctoral researcher. A lack of evolutionary plasticity in maximal aerobic speed is hypothesized to limit further increase in wheel running. Effects of both increased and decreased oxygen on wheel running and on maximal oxygen consumption will be studied. The energetic cost of locomotion will be measured during both wheel and treadmill running. Lung diffusing capacity will be estimated morphometrically. Components of the skeleton will be examined for differences in size, shape, symmetry, and amount of secondary remodeling. Myosin heavy-chain isoform expression will be quantified in hindlimb muscle, and the "mighty mini-muscles" that occur in two of the selected lines will be characterized biochemically and by electron microscopy. For many of the above-mentioned traits, both genetic and phenotypic plasticity, and potential interactions, will be examined by measuring S and C mice that have been housed chronically with or without wheel access. Immunocytochemistry with cFos as an indicator of neuronal activity will be used to compare key brain regions in S and C mice at rest and during peak wheel running (motivation, reward, & addiction; voluntary control of movement; spatial memory & learning). Results will lead to a comprehensive understanding of how increased activity levels evolve in a model mammalian system. Mice will be made available to other researchers and they will be an important model for studying effects of exercise on physical fitness, health, and aging.