Rats selectively-bred for low and high voluntary running: co-selected traits and the effects of voluntary running on the dentate gyrus transcriptome
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The Booth lab at the University of Missouri has selectively-bred Wistar rats for low (LVR) and high (HVR) voluntary running behavior as a model for examining the genetic and physiological origins of physical activity motivation. The major advantage of selective breeding over non-natural methods of genetic engineering is the perpetuation of naturally-existing, polygenic milieus that dictate complex behaviors or phenotypes (e.g. motivation to be physically active, etiology of obesity). Since most genes and physiological systems are pleiotropic and function as modular networks, a "by-product" of selective breeding is the co-selection of traits sharing some common genetic origins with the selected trait. Overall, the major emphasis of my dissertation was two-fold: (1) the elucidation of behavioral traits co-selected with low and high physical activity motivational behavior and (2) the effect of voluntary running in a mildly stressful environment on the dentate gyrus transcriptome of rats selectively bred for low voluntary running. Emphasis 1 (Chapters 2 and 3) was approached by measuring the performance of LVR and HVR rats in behavioral tests classically designed to measure non-wheel running locomotor activity behavior (i.e. open field test), sensitivity to drugs of abuse (i.e. cocaine-induced locomotor activity), anxiety-like behavior (i.e. elevated plus maze), depressive-like behavior (i.e. forced swim test), and nociception (i.e. thermal and mechanical stimulus). Emphasis 2 was approached by using RNA sequencing (RNA-seq) to map the transcriptome of the dentate gyrus after exposing sedentary and wheel running LVR and WT rats to 5 weeks of chronic mild stress (CMS). The results from Chapters 2 and 3 demonstrate that LVR and HVR rats have co-selected other behaviors, which suggest that they may be a valuable model for an array of research disciplines including: (1) the investigation of the genetic basis for physical activity motivation, (2) hyperactivity, (3) sensitivity to drugs of abuse (e.g. addiction), (4) emotional/stress disorders (e.g. anxiety and depression), and (5) nociception as well as the interactions between these complex phenotypes. The results from Chapter 4 provide transcriptomic evidence that low amounts of voluntary running performed by female LVR rats in a CMS environment are sufficient for eliciting robust changes in dentate gyrus transcriptome that included gene expression signatures associated with elevated synaptic plasticity, improved memory function, and increased blood vessel development.
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