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- Member of: ASU Electronic Theses and Dissertations
Description
Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Taylor, Sara (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
Description
The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD.
ContributorsHoffman, Ann (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Hammer, Jr., Ronald P. (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2013
Description
Consideration of both biological and human-use dynamics in coupled social-ecological systems is essential for the success of interventions such as marine reserves. As purely human institutions, marine reserves have no direct effects on ecological systems. Consequently, the success of a marine reserve depends on managers` ability to alter human behavior in the direction and magnitude that supports reserve objectives. Further, a marine reserve is just one component in a larger coupled social-ecological system. The social, economic, political, and biological landscape all determine the social acceptability of a reserve, conflicts that arise, how the reserve interacts with existing fisheries management, accuracy of reserve monitoring, and whether the reserve is ultimately able to meet conservation and fishery enhancement goals. Just as the social-ecological landscape is critical at all stages for marine reserve, from initial establishment to maintenance, the reserve in turn interacts with biological and human use dynamics beyond its borders. Those interactions can lead to the failure of a reserve to meet management goals, or compromise management goals outside the reserve. I use a bio-economic model of a fishery in a spatially patchy environment to demonstrate how the pre-reserve fisheries management strategy determines the pattern of fishing effort displacement once the reserve is established, and discuss the social, political, and biological consequences of different patterns for the reserve and the fishery. Using a stochastic bio-economic model, I demonstrate how biological and human use connectivity can confound the accurate detection of reserve effects by violating assumptions in the quasi-experimental framework. Finally, I examine data on recreational fishing site selection to investigate changes in response to the announcement of enforcement of a marine reserve in the Gulf of California, Mexico. I generate a scale of fines that would fully or partially protect the reserve, providing a data-driven way for managers to balance biological and socio-economic goals. I suggest that natural resource managers consider human use dynamics with the same frequency, rigor, and tools as they do biological stocks.
ContributorsFujitani, Marie (Author) / Abbott, Joshua (Thesis advisor) / Fenichel, Eli (Thesis advisor) / Gerber, Leah (Committee member) / Anderies, John (Committee member) / Arizona State University (Publisher)
Created2014
Description
Evidence from the 20th century demonstrated that early life stress (ELS) produces long lasting neuroendocrine and behavioral effects related to an increased vulnerability towards psychiatric illnesses such as major depressive disorder, post-traumatic stress disorder, schizophrenia, and substance use disorder. Substance use disorders (SUDs) are complex neurological and behavioral psychiatric illnesses. The development, maintenance, and relapse of SUDs involve multiple brain systems and are affected by many variables, including socio-economic and genetic factors. Pre-clinical studies demonstrate that ELS affects many of the same systems, such as the reward circuitry and executive function involved with addiction-like behaviors. Previous research has focused on cocaine, ethanol, opiates, and amphetamine, while few studies have investigated ELS and methamphetamine (METH) vulnerability. METH is a highly addictive psychostimulant that when abused, has deleterious effects on the user and society. However, a critical unanswered question remains; how do early life experiences modulate both neural systems and behavior in adulthood? The emerging field of neuroepigenetics provides a potential answer to this question. Methyl CpG binding protein 2 (MeCP2), an epigenetic tag, has emerged as one possible mediator between initial drug use and the transition to addiction. Additionally, there are various neural systems that undergo long lasting epigenetics changes after ELS, such as the response of the hypothalamo-pituitary-adrenal (HPA) axis to stressors. Despite this, little attention has been given to the interactions between ELS, epigenetics, and addiction vulnerability. The studies described herein investigated the effects of ELS on METH self-administration (SA) in adult male rats. Next, we investigated the effects of ELS and METH SA on MeCP2 expression in the nucleus accumbens and dorsal striatum. Additionally, we investigated the effects of virally-mediated knockdown of MeCP2 expression in the nucleus accumbens core on METH SA, motivation to obtain METH under conditions of increasing behavioral demand, and reinstatement of METH-seeking in rats with and without a history of ELS. The results of these studies provide insights into potential epigenetic mechanisms by which ELS can produce an increased vulnerability to addiction in adulthood. Moreover, these studies shed light on possible novel molecular targets for treating addiction in individuals with a history of ELS.
ContributorsLewis, Candace (Author) / Olive, M. Foster (Thesis advisor) / Hammer, Ronald (Committee member) / Neisewander, Janet (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2015
Description
The Energiewende aims to drastically reduce Germany’s greenhouse gas emissions, without relying on nuclear power, while maintaining a secure and affordable energy supply. Since 2000 the country’s renewable-energy share has increased exponentially, accounting in 2017 for over a third of Germany's gross electricity consumption. This unprecedented achievement is the result of policies, tools, and institutional arrangements intended to steer society to a low-carbon economy. Despite its resounding success in renewable-energy deployment, the Energiewende is not on track to meet its decarbonization goals. Energiewende rules and regulations have generated numerous undesired consequences, and have cost much more than anticipated, a burden borne primarily by energy consumers. Why has the Energiewende not only made energy more expensive, but also failed to bring Germany closer to its decarbonization goals? I analyzed the Energiewende as a complex socio-technical system, examining its legal framework and analyzing the consequences of successive regulations; identifying major political and energy players and the factors that motivated them to pursue socio-technical change; and documenting the political trends and events in which the Energiewende is rooted and which continue to shape it. I analyzed the dynamics and the loopholes that created barriers to transition, pushed the utility sector to the brink of dissolution, and led to such undesirable outcomes as negative wholesale prices and forced exports of electricity to Germany’s European neighbors. Thirty high-level energy experts and stakeholders were interviewed to find out how the best-informed members of German society perceive the Energiewende. Surprisingly, although they were highly critical of the way the transition has unfolded, most were convinced that the transition would eventually succeed. But their definitions of success did not always depend on achieving carbon-mitigation targets. Indeed, Germany jeopardizes the achievement of these targets by changing too many policy and institutional variables at too fast a pace. Good intentions and commitment are not enough to create economies based on intermittent energy sources: they will also require intensive grid expansion and breakthroughs in storage technology. The Energiewende demonstrates starkly that collective action driven by robust political consensus is not sufficient for steering complex socio-technical systems in desired directions.
ContributorsSturm, Christine (Author) / Sarewitz, Daniel (Thesis advisor) / Miller, Clark (Committee member) / Anderies, John (Committee member) / Hirt, Paul (Committee member) / Arizona State University (Publisher)
Created2018
Description
The plateau pika (Ochotona curzoniae), a small burrowing lagomorph that occupies the high alpine grassland ecosystems of the Qinghai-Tibetan Plateau in western China, remains a controversial subject among policymakers and researchers. One line of evidence points to pikas being a pest, which has led to massive attempts to eradicate pika populations. Another point of view is that pikas are a keystone species and an ecosystem engineer in the grassland ecosystem of the QTP. The pika eradication program raises a difficult ethical and religious dilemma for local pastoralists, and is criticized for not being supported by scientific evidence. Complex interactions between pikas, livestock, and habitat condition are poorly understood. My dissertation research examines underpinning justifications of the pika poisoning program leading to these controversies. I investigated responses of pikas to habitat conditions with field experimental manipulations, and mechanisms of pika population recovery following pika removal. I present policy recommendations based on an environmental ethics framework and findings from the field experiments. After five years of a livestock grazing exclusion experiment and four years of pika monitoring, I found that grazing exclusion resulted in a decline of pika habitat use, which suggests that habitat conditions determine pika population density. I also found that pikas recolonized vacant burrow systems following removal of residents, but that distances travelled by dispersing pikas were extremely short (~50 m). Thus, current pika eradication programs, if allowed to continue, could potentially compromise local populations as well as biodiversity conservation on the QTP. Lethal management of pikas is a narrowly anthropocentric-based form of ecosystem management that has excluded value-pluralism, such as consideration of the intrinsic value of species and the important ecological role played by pikas. These conflicting approaches have led to controversies and policy gridlock. In response, I suggest that the on-going large-scale pika eradication program needs reconsideration. Moderation of stocking rates is required in degraded pika habitats, and Integrated Pest Management may be required when high stocking rate and high pika density coexist. A moderate level of livestock and pika density can be consistent with maintaining the integrity and sustainability of the QTP alpine steppe ecosystem.
ContributorsBadingqiuying (Author) / Smith, Andrew T. (Thesis advisor) / Wu, Jianguo (Committee member) / Minteer, Ben (Committee member) / Anderies, John (Committee member) / Harris, Richard B. (Committee member) / Arizona State University (Publisher)
Created2016