Influence of Acute and Chronic Exercise on Markers of Hippocampal Plasticity

Exercise and physical activity are lifestyle behaviors associated with enriched mental health. Understanding the mechanisms by which exercise and physical activity improve mental health may provide insight for novel therapeutic approaches for numerous mental health disorders. This dissertation reports the findings from three studies investigating the influence of acute and chronic exercise on behavioral and mechanistic markers of hippocampal plasticity and delves into the potential role of noradrenergic signaling in the hippocampal adaptations with exercise. The first study assessed the effects of long-term voluntary wheel running on hippocampal expression of plasticity-associated genes and proteins in adult male and female C57BL/6J mice, highlighting sex differences in the adaptations to long-term voluntary wheel running. The second study examined the influence of acute exercise intensity on AMPA receptor phosphorylation, a mechanism essential for hippocampal plasticity, plasticity- associated gene expression, spatial learning and memory, and anxiety-like behavior. The unexpected finding that acute exercise increased anxiety-like behavior encouraged investigation into the role of central noradrenergic signaling in acute exercise-induced anxiety. The third study determined how previous exposure to voluntary wheel running modulates the response to an acute bout of exercise, focusing primarily on transcription of the important plasticity-promoting gene, brain-derived neurotrophic factor. Using a pharmacological approach to compromise the locus coeruleus noradrenergic system, a system that is implicated in age-related mental health disorders such as Alzheimer’s Disease, the third study also investigated the influence and interaction of the noradrenergic system and acute exercise on expression of multiple brain-derived neurotrophic factor transcripts. Together, this dissertation reports the findings from a series of experiments that explored similarities, differences, and interactions between the effects of acute and chronic exercise on markers of hippocampal plasticity and behavior. Further, this work provides insight into the role of the noradrenergic system in exercise-induced hippocampal plasticity.

THE INFLUENCE OF URBAN FORM AT DIFFERENT GEOGRAPHICAL SCALES ON TRAVEL BEHAVIOR; EVIDENCE FROM U.S. CITIES

Suburban lifestyle is popular among American families, although it has been criticized for encouraging automobile use through longer commutes, causing heavy traffic congestion, and destroying open spaces (Handy, 2005). It is a serious concern that people living in low-density suburban areas suffer from high automobile dependency and lower rates of daily physical activity, both of which result in social, environmental and health-related costs. In response to such concerns, researchers have investigated the inter-relationships between urban land-use pattern and travel behavior within the last few decades and suggested that land-use planning can play a significant role in changing travel behavior in the long-term. However, debates regarding the magnitude and efficiency of the effects of land-use on travel patterns have been contentious over the years. Changes in built-environment patterns is potentially considered a long-term panacea for automobile dependency and traffic congestion, despite some researchers arguing that the effects of land-use on travel behavior are minor, if any. It is still not clear why the estimated impact is different in urban areas and how effective a proposed land-use change/policy is in changing certain travel behavior. This knowledge gap has made it difficult for decision-makers to evaluate land-use plans and policies. In addition, little is known about the influence of the large-scale built environment. In the present dissertation, advanced spatial-statistical tools have been employed to better understand and analyze these impacts at different scales, along with analyzing transit-oriented development policy at both small and large scales. The objective of this research is to: (1) develop scalable and consistent measures of the overall physical form of metropolitan areas; (2) re-examine the effects of built-environment factors at different hierarchical scales on travel behavior, and, in particular, on vehicle miles traveled (VMT) and car ownership; and (3) investigate the effects of transit-oriented development on travel behavior. The findings show that changes in built-environment at both local and regional levels could be very influential in changing travel behavior. Specifically, the promotion of compact, mixed-use built environment with well-connected street networks reduces VMT and car ownership, resulting in less traffic congestion, air pollution, and energy consumption.

THE INFLUENCE OF MOTIVATION ON EMOTION REGULATION AND MOTOR PERFORMANCE: EXAMINATION OF A NEURO-AFFECTIVE MODEL

Mental stress is known to disrupt the execution of motor performance and can lead to decrements in the quality of performance, however, individuals have shown significant differences regarding how fast and well they can perform a skilled task according to how well they can manage stress and emotion. The purpose of this study was to advance our understanding of how the brain modulates emotional reactivity under different motivational states to achieve differential performance in a target shooting task that requires precision visuomotor coordination. In order to study the interactions in emotion regulatory brain areas (i.e. the ventral striatum, amygdala, prefrontal cortex) and the autonomic nervous system, reward and punishment interventions were employed and the resulting behavioral and physiological responses contrasted to observe the changes in shooting performance (i.e. shooting accuracy and stability of aim) and neuro-cognitive processes (i.e. cognitive load and reserve) during the shooting task. Thirty-five participants, aged 18 to 38 years, from the Reserve Officers’ Training Corp (ROTC) at the University of Maryland were recruited to take 30 shots at a bullseye target in three different experimental conditions. In the reward condition, $1 was added to their total balance for every 10-point shot. In the punishment condition, $1 was deducted from their total balance if they did not hit the 10-point area. In the neutral condition, no money was added or deducted from their total balance. When in the reward condition, which was reportedly most enjoyable and least stressful of the conditions, heart rate variability was found to be positively related to shooting scores, inversely related to variability in shooting performance and positively related to alpha power (i.e. less activation) in the left temporal region. In the punishment (and most stressful) condition, an increase in sympathetic response (i.e. increased LF/HF ratio) was positively related to jerking movements as well as variability of placement (on the target) in the shots taken. This, coupled with error monitoring activity in the anterior cingulate cortex, suggests evaluation of self-efficacy might be driving arousal regulation, thus affecting shooting performance. Better performers showed variable, increasing high-alpha power in the temporal region during the aiming period towards taking the shot which could indicate an adaptive strategy of engagement. They also showed lower coherence during hit shots than missed shots which was coupled with reduced jerking movements and better precision and accuracy. Frontal asymmetry measures revealed possible influence of the prefrontal lobe in driving this effect in reward and neutral conditions. The possible interactions, reasons behind these findings and implications are discussed.