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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

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
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Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind

Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind the improvements in hippocampal mediated cognition when chronic stress ends and a post-stress rest period is given. Consequently, the goal of this dissertation is to uncover the mechanisms that allow for spatial ability to improve in the aftermath of chronic stress. In chapter 2, the protein brain derived neurotrophic factor (BDNF) was investigated as a mechanism that allows for spatial ability to show improvements following the end of chronic stress. It was found that decreasing the expression of BDNF in the hippocampus prevented spatial memory improvements following a post-stress rest period. Chapter 3 was performed to determine whether hippocampal CA3 apical dendritic complexity requires BDNF to show improvements following a post-stress rest period, and whether a receptor for BDNF, TrkB, mediates the improvements of spatial ability and dendritic complexity in a temporal manner, i.e. during the rest period only. These experiments showed that decreased hippocampal BDNF expression prevented improvements in dendritic complexity, and administration of a TrkB antagonist during the rest period also prevented the improvements in spatial ability and dendritic complexity. In chapter 4, the role of the GABAergic system on spatial ability following chronic stress and a post-stress rest period was investigated. Following chronic stress, it was found that male rats showed impairments on the acquisition phase of the RAWM and this correlated with limbic glutamic acid decarboxylase, a marker for GABA. In chapter 5, a transgenic mouse that expresses a permanent marker on all GABAergic interneurons was used to assess the effects of chronic stress and a post-stress rest period on hippocampal GABAergic neurons. While no changes were found on the total number of GABAergic interneurons, specific subtypes of GABAergic interneurons were affected by stressor manipulations. Collectively, these studies reveal some mechanisms behind the plasticity seen in the hippocampus in response to a post-stress rest period.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Newbern, Jason M. (Committee member) / Orchinik, Miles (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2018
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The goal of the present study was to investigate whether a rest period following the end of chronic stress would impact fear extinction. Past research has indicated that chronic stress leads to impairments in the learning and recall of fear conditioning extinction. Moreover, the effects of chronic stress

The goal of the present study was to investigate whether a rest period following the end of chronic stress would impact fear extinction. Past research has indicated that chronic stress leads to impairments in the learning and recall of fear conditioning extinction. Moreover, the effects of chronic stress can return to levels similar to controls when a post-stress “rest” period (i.e., undisturbed except for normal husbandry) is given prior to testing. Male rats underwent chronic restraint stress for 6hr/day/21days (STR-IMM). Some rats, underwent a post-stress rest period for 6- or 3-weeks after the end of stress (STR-R6, STR-R3). Control (CON) rats were unrestrained for the duration of the experiment. In Experiment 1, following the stress or rest manipulation, all rats were acclimated to conditioning and extinction contexts, fear conditioned with 3 tone-foot shock pairings, and then had two days of extinction training. All groups froze similarly to the tone across all training sessions. However, STR-R6/R3 froze less in the non-shock context than did STR-IMM or CON. During extinction training, STR-IMM showed high levels of freezing to the non-shock context, leading to a concern they may be generalizing across contexts. Consequently, a follow-up experiment tested for context generalization. In Experiment 2, STR-IMM rats underwent a generalization test in an environment that was either different or the same as the conditioning environment, using STR-R6 as a comparison. STR-IMM and STR-R6 showed similar relative levels of freezing to tone and context, regardless of their conditioning environment to reveal that STR-IMM did not generalize and instead, maybe expressing hypervigilance. Thus, the present study demonstrated the novel finding that a rest period from chronic stress can lead to reduced fear responsiveness in a non-shock environment.
ContributorsJudd, Jessica M (Author) / Conrad, Cheryl D. (Thesis advisor) / Sanabria, Federico (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Timing performance is sensitive to fluctuations in time and motivation, thus interval timing and motivation are either inseparable or conflated processes. A behavioral systems model (e.g., Timberlake, 2000) of timing performance (Chapter 1) suggests that timing performance in externally-initiated (EI) procedures conflates behavioral modes differentially sensitive to motivation, but that

Timing performance is sensitive to fluctuations in time and motivation, thus interval timing and motivation are either inseparable or conflated processes. A behavioral systems model (e.g., Timberlake, 2000) of timing performance (Chapter 1) suggests that timing performance in externally-initiated (EI) procedures conflates behavioral modes differentially sensitive to motivation, but that response-initiated (RI) procedures potentially dissociate these behavioral modes. That is, timing performance in RI procedures is expected to not conflate these behavioral modes. According to the discriminative RI hypothesis, as initiating-responses become progressively discriminable from target responses, initiating-responses increasingly dissociate interval timing and motivation. Rats were trained in timing procedures in which a switch from a Short to a Long interval indexes timing performance (a latency-to-switch, LTS), and were then challenged with pre-feeding and extinction probes. In experiments 1 (Chapter 2) and 2 (Chapter 3), discriminability of initiating-responses was varied as a function of time, location, and form for rats trained in a switch-timing procedure. In experiment 3 (Chapter 4), the generalizability of the discriminative RI hypothesis was evaluated in rats trained in a temporal bisection procedure. In experiment 3, but not 1 and 2, RI enhanced temporal control of LTSs relative to EI. In experiments 1 and 2, the robustness of LTS medians to pre-feeding but not extinction increased with the discriminability of initiating-responses from target responses. In experiment 3, the mean LTS was robust to pre-feeding in EI and RI. In all three experiments, pre-feeding increased LTS variability in EI and RI. These results provide moderate support for the discriminative RI hypothesis, indicating that initiating-responses selectively and partially dissociate interval timing and motivation processes. Implications for the study of cognition and motivation processes are discussed (Chapter 5).
ContributorsDaniels, Carter W (Author) / Sanabria, Federico (Thesis advisor) / McClure, Samuel M. (Committee member) / Wynne, Clive D.L. (Committee member) / Olive, Michael F. (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Given its impact on the accounting profession and public corporations, Sarbanes-Oxley Act of 2002(SOX) is a widely researched regulation among accounting scholars. Research typically focuses on the impact it has had on corporations, executives and auditors, however, there is limited research that illustrates the impact SOX may have on average

Given its impact on the accounting profession and public corporations, Sarbanes-Oxley Act of 2002(SOX) is a widely researched regulation among accounting scholars. Research typically focuses on the impact it has had on corporations, executives and auditors, however, there is limited research that illustrates the impact SOX may have on average Americans. There were several US criminal code sections that resulted from the passing of SOX. Statute 1519, which is often referred to as the "anti-shredding provision", penalizes anyone who "knowingly alters, destroys, mutilates, conceals, covers up, falsifies, or makes a false entry in any record, document, or tangible object with the intent to" obstruct a current or foreseeable federal investigation. This statute, although intended to punish behavior similar to that which occurred in the early 2000s by corporations and auditors, has been used to charge people beyond its original intent. Several issues with the crafting of the statute cause its broad application and some litigation even reached the Supreme Court due to its vague wording. Not only is the statute being applied beyond the intent, there are other issues that legal scholars have critiqued it for. This statute is far from being the only law facing these issues as the same issues and critiques are found in the 14th amendment. Rewriting the statute seems to be the most effective way to address the concerns of judges, lawyers and defendants regarding the statute. In addition, Congress could have passed this statute outside of SOX to avoid being seen as overreaching if obstruction of justice related to documents was actually an issue outside of corporate fraud.
ContributorsGonzalez, Joana (Author) / Samuelson, Melissa (Thesis director) / Lowe, Jordan (Committee member) / School of Accountancy (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
The present study examined how systemic low doses of nicotine affect the microstructure of food-reinforced behavior in rats. Rats were given an acute saline or nicotine treatment (0.1-0.6 mg/kg, resting at least 48 h between injections), and a chronic saline or nicotine treatment (0.3 mg/kg for 10 consecutive days). Immediately

The present study examined how systemic low doses of nicotine affect the microstructure of food-reinforced behavior in rats. Rats were given an acute saline or nicotine treatment (0.1-0.6 mg/kg, resting at least 48 h between injections), and a chronic saline or nicotine treatment (0.3 mg/kg for 10 consecutive days). Immediately after treatment, rats were required to press a lever to obtain food, whose availability was unpredictable, but programmed at a constant rate (on average every 80 s). Acute nicotine dose-dependently suppressed behavior prior to the delivery of the first reinforcer, but enhanced food-reinforced behavior afterwards. This effect was primarily observed in the time it took rats to initiate food-seeking behavior, and not in the food-seeking behavior itself. A pre-feeding control procedure suggests that these effects cannot be explained only by changes in appetite. Over the course of chronic nicotine exposure, tolerance developed to the suppressive, but not to the enhancing effects of nicotine on food-seeking behavior. These results suggest that ostensive sensitization effects of nicotine on behavior may instead reflect a tolerance for its suppressive effects on behavior.
ContributorsRomero, Korinna Estela (Author) / Sanabria, Federico (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / Bevins, Rick (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
The capacity to track time in the seconds-to-minutes range, or interval timing, appears to be at least partially dependent on intact hippocampal (HPC) function. The current dissertation sought to dissociate timed responses, non-timed responses, and motivational aspects of behavior in order to propose a role of the HPC in specific

The capacity to track time in the seconds-to-minutes range, or interval timing, appears to be at least partially dependent on intact hippocampal (HPC) function. The current dissertation sought to dissociate timed responses, non-timed responses, and motivational aspects of behavior in order to propose a role of the HPC in specific timing sub-processes. In Chapter 2, effects of dorsal HPC (dHPC) lesions on temporal responding in a switch-timing task revealed a critical role of dHPC in the acquisition of interval timing criteria. Following dHPC lesions, the start time of responding was systemically shortened, in a manner that was enhanced and sustained when encoding a novel long interval, consistent with a memory-based account of dHPC function in timed responding. Chapter 3 investigated effects of chronic stress, which has been shown to reliably induce HPC dendritic retraction, on interval timing, utilizing response-initiated schedules of reinforcement, which facilitate deconvolution of timing and motivation. This revealed task-dependent effects on interval timing and motivation, where stress induced transient effects on motivation in a prospective timing task, but transient effects on the variability of timed responding in a retrospective timing task, consistent with an effect on memory function in interval timing. Chapter 4 sought to bring timed responding, motivation, and non-timed behaviors under stronger procedural control, through the implementation of a response-initiated timing-with-opportunity-cost task, in which a cost is imposed on temporal food-seeking by the presence of a concurrent source of probabilistic reinforcement. This arrangement garnered strong schedule control of behavior, and revealed individual-subject differences in the effects of reward devaluation, such that it affected motivation in some rats, but temporal responding in others. Using this methodology, Chapter 5 investigated initial temporal entrainment of behavior under pharmacological deactivation of dHPC and revealed its critical involvement in updating memory to new temporal contingencies. Together, data from this dissertation contrast with prior conclusions that the HPC is not involved in learning temporal criteria, and instead suggest that its function is indeed critical to encoding temporal intervals in memory.
ContributorsGupta, Tanya A. (Author) / Sanabria, Federico (Thesis advisor) / Conrad, Cheryl (Committee member) / Olive, Foster (Committee member) / McClure, Samuel (Committee member) / Arizona State University (Publisher)
Created2022
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Description
This paper consists of a literature review, wherein four papers surrounding Motivation Crowding Theory (MCT) were read and analyzed. The paper then goes into an analysis of a survey I conducted. The survey consisted of three main questions with three sub-questions for each, and all attempted to find a "limit"

This paper consists of a literature review, wherein four papers surrounding Motivation Crowding Theory (MCT) were read and analyzed. The paper then goes into an analysis of a survey I conducted. The survey consisted of three main questions with three sub-questions for each, and all attempted to find a "limit" to MCT. However, results for the survey were ultimately inconclusive. The paper concludes with lessons learned in conducting research and surveys in particular, as well as a nod to the relevancy of MCT in business and personal applications.
ContributorsSmith, Mallory Anne (Author) / Reckers, Phil (Thesis director) / Samuelson, Melissa (Committee member) / Lowe, Jordan (Committee member) / School of Accountancy (Contributor) / Department of Information Systems (Contributor) / WPC Graduate Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05