Any type of locomotion requires central activation of motor systems, which can be suppressed by neurochemicals in a phenomena known as Central Fatigue (CF). Resistance to CF may evolve to support extreme locomotor abilities and may also occur in response to exercise training (phenotypic plasticity). I used the High-Runner (HR) mouse model to study CF in four replicate lines that have evolved in response to many generations of selective breeding for voluntary wheel running.

Serotonin is the most studied neurotransmitter in relation to CF. In my work, a serotonin inhibitory autoreceptor antagonist decreased endurance during forced treadmill exercise in HR mice, but not in mice from four non-selected Control (C) lines. Wheel running decreased in HR but not C mice at the highest dose of a serotonin agonist, but was unaffected by the antagonist. Therefore, serotonin signaling affects performance of both forced and voluntary exercise in a genotype-dependent manner.

I also tested effects of sports drinks and caffeine. Red Bull increased distance run voluntarily on wheels in both HR and C lines, but not did caffeine alone in water. Neither Red Bull nor caffeine significantly affected maximal aerobic capacity (VO2max), but both reduced post-trial tiredness. Gatorade did not affect wheel running or endurance in either line type. These results suggest that caffeine increases voluntary exercise levels of mice via effects on motivation or fatigue resistance, but not VO2max.

Finally, I analyzed strides of both sexes of HR and C mice on a motorized treadmill at speeds relevant to wheel running. Stance width was narrower in HR than C, and paw contact area and duty factor were greater in mini-muscle individuals (subset of HR mice with 50% reduced hindlimb muscle mass) than in normal-muscled HR or C. Many stride characteristics were affected by six days of wheel access. Thus, stride characteristics are responsive to selective breeding for locomotor behavior and exhibit phenotypic plasticity.

In conclusion, HR mice have evolved neurobiologically to resist serotonin-mediated CF, and morphologically and/or behaviorally to have a narrower stance. These results parallel wild animals that have evolved for, and humans that train for, extreme locomotor performance.

Neurocysticercosis (NCC), a parasitic infection of the human central nervous system with the organism Taenia solium is an important, yet neglected, global public health problem causing preventable disability such as seizure and stroke in those infected. NCC symptoms vary widely, based upon the number and location of lesions, and can be difficult to identify and diagnose. NCC is a reportable disease in Los Angeles County. However, there is limited understanding of NCC disease burden in Los Angeles County due to reporting barriers.

This dissertation is presented in three papers. The first paper examines case reporting and demographics of probable NCC cases identified in a Los Angeles community hospital through review of computerized tomography (CT) brain scan reports performed during 2012 that describe evidence of lesions highly suggestive of NCC infection. The study identified 303 probable NCC cases and found that 7 of the 11 cases reported to Los Angeles County Department of Public Health in 2012 were from the study site.

The second paper describes the presenting symptoms and mortality data of identified probable NCC cases. The study found that 3.9% of cases presented with seizure upon admission to the hospital and that death occurred in 3.9% of cases. The most common presenting symptom was headache (24.7%).

The third paper analyzes the rate of prior and acute stroke in the 303 probable NCC cases. The study found that 28.3% had evidence of prior stroke and 13.2% had evidence of acute stroke on CT brain scan performed during their admission to the hospital. NCC infection was also shown to be statistically significant as an independent risk factor for acute stroke when other known stroke risk factors were controlled for. The odds of acute stroke for probable NCC-infected persons were nearly 25 times that of noninfected NCC persons in this study.

The research presented here improves the understanding of NCC disease burden in Los Angeles County, demonstrates differences in NCC presenting symptoms, and demonstrates that NCC infection is an independent risk factor for acute stroke.

Elucidating genetic and environmental factors that affect physical activity, dietary choices, and their interactions is essential for attempts to ameliorate the obesity epidemic. Using mice selectively bred for high voluntary wheel-running behavior (four replicate HR lines) and their four non-selected control (C) lines, I investigated early-life effects on adult physical activity, preference for Western diet (WD), and whole-animal metabolic rate and fuel usage with WD.

Early-life access to wheels increased adult wheel running but had no statistical effect on spontaneous physical activity (SPA) of adult males in their attached home cages. The early-exercise effect on wheel running disappeared after one week, but body mass was reduced throughout the experiment. Early-life exercise reduced circulating leptin concentrations in HR lines, but increase them in C lines (genotype-by-environment interaction).

Both HR and C mice highly preferred WD, high in fat and sucrose, over standard chow. After 17 days of wheel acclimation, but not after six days, HR had a stronger preference for WD than did C mice, which further increased their wheel running and decreased their SPA. When a separate set of mice was switched from standard chow to WD, the effects on wheel running depended on both sex and linetype in a complicated fashion.

Fuel usage was studied indirectly by whole-animal respirometry. Female HR and C mice did not differ statistically in minimal resting metabolic rate, but the former had higher levels of maximal oxygen consumption during voluntary wheel running. Contrary to my hypothesis, I found no evidence for a reduced respiratory exchange ratio (which would indicate greater reliance on lipids) in HR mice at rest, during maximal voluntary exercise or measured over a 23-hour period, either on standard chow or with WD.

Overall, my research provides evidence for important, genetically based differences between the HR and C lines, sex differences, and sex-by-linetype interactions. These results encourage use of the HR mice as an anti-obesity model in further studies of the complex physiological and neurobiological mechanisms that interact with sex and genetic background in ways that may allow some individuals to resist the adverse effects of obesogenic environments.

Some of the most compelling traits to evolutionary biologists are sexually selected traits. The `un-natural' expression of these traits has puzzled biologists since the time of Charles Darwin. Why would a trait evolve that seems to decrease survival? Most of these traits evolve because they increase the reproductive fitness of the bearer, either through intra-sexual or inter-sexual competition. However, these sexually selected traits must meet the demands of both natural and sexual selection. It is therefore assumed that there are `costs' associated with the trait that limits their expression. In this dissertation I examined the performance costs of a sexually selected trait, expressed as an exaggerated morphological structure.

I first introduce a more integrative approach to the study of detecting costs of sexually selected traits. This approach incorporates additional aspects of the organism's phenotype that may have evolved to offset the costs of the sexually selected trait. I show that ignoring these `compensatory' traits may mask the cost of the sexually selected trait using synthesized data.

I then set out to examine the repeatability of various swimming performance measures. Using male guppies (Poecilia reticulata) I demonstrate that swimming performance measures are stable over various time scales. Both aerobic and anaerobic locomotor functions were examined over time scales varying from days to more than a year later. While most performance measures were not stable over a year, at least one was repeatable. Furthermore, although most performance measures decreased over a year, one significantly increased (maximum speed, U_max).

I then used phylogenetic comparative methods to determine the locomotor costs of the sexually selected `sword' among species of Xiphophorus and Priapella, taking into account compensatory traits. I showed that inter-specifically, the sword is not a cost to critical swimming speed among 19 species of Xiphophorus and Priapella. In fact, when compensatory traits and phylogenetic information are included, the sword had a significant positive effect on critical swimming speed among these species. This suggests that as this sexually selected trait evolved it was not a locomotor handicap.