Rats selectively-bred for low and high voluntary running: co-selected traits and the effects of voluntary running on the dentate gyrus transcriptome

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI-COLUMBIA 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.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Medical pharmacology and physiology (MU)

Grantor dc:publisher

University of Missouri--Columbia

Year dc:date.issued

2014

Author dc:creator

• Brown, Jacob Daniel

Advisor dc:contributor.advisor

• Booth, Frank W.

Statement dc:rights

• Access to files is limited to the University of Missouri--Columbia with SSO login.

Language dc:language.iso

eng, English

DOI

https://doi.org/10.32469/10355/45845

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/45845