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- Creators: Arizona State University
- Creators: Olive, M. Foster
Description
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
In the past decade, research has demonstrated the relationship between higher levels of self-compassion and lower levels of negative psychological outcomes. More recently, the concept of self-compassion has been explored within the context of various health behaviors. Very few studies have investigated the potential relationship between self-compassion and eating behaviors. Based on literature and the established relationship between negative self-evaluation and abnormal eating behaviors/eating disorders, the current study sought to examine correlations between self-compassion, eating behaviors, and stress in first time college freshmen. The study population consisted of 1478 participants; ages 18-22 years; females = 936 (63%), males = 541 (37%). Participants self-reported measures of the Perceived Stress Scale (PSS), the Three Factor Eating Questionnaire (TFEQ), and the Self Compassion Scale (SCS). PSS score, the overall score and individual subscale scores of SCS, and the three subscale scores of the TFEQ (restraint, disinhibiton, hunger) were examined with Pearson correlations. Results of this study indicate significant (p = < .05) differences between males and females in PSS and all three negative SCS subscales. There was a strong and consistent correlation between the eating behavior of disinhibition and all three negative constructs of self-compassion (self-judgment, r = .29; isolation, r = .23; over-identification, r = .28) in females. The eating behavior of restraint was similarly correlated with SCS self-judgment in females (r = .26). More research is needed to understand differences in stress, self-compassion, and eating behaviors between males and females and to better comprehend the weak associations between eating behaviors and the positive psychological constructs of self-compassion (self-kindness, common humanity, and mindfulness) for males and females. Additionally, future research should focus on the three subscales of disinhibition as they relate to the negative constructs of self-compassion. The preliminary results of this study suggest it would be beneficial, particularly to female college freshmen, to more fully understand the dynamics of the relationship between eating behaviors and self-compassion; this knowledge may help to better structure appropriate coping strategies for the prevention of disordered eating behaviors.
ContributorsJames, Darith (Author) / Sebren, Ann (Thesis advisor) / Swan, Pamela D. (Committee member) / Der Ananian, Cheryl (Committee member) / Arizona State University (Publisher)
Created2013
Description
Specific dendritic morphologies are a hallmark of neuronal identity, circuit assembly, and behaviorally relevant function. Despite the importance of dendrites in brain health and disease, the functional consequences of dendritic shape remain largely unknown. This dissertation addresses two fundamental and interrelated aspects of dendrite neurobiology. First, by utilizing the genetic power of Drosophila melanogaster, these studies assess the developmental mechanisms underlying single neuron morphology, and subsequently investigate the functional and behavioral consequences resulting from developmental irregularity. Significant insights into the molecular mechanisms that contribute to dendrite development come from studies of Down syndrome cell adhesion molecule (Dscam). While these findings have been garnered primarily from sensory neurons whose arbors innervate a two-dimensional plane, it is likely that the principles apply in three-dimensional central neurons that provide the structural substrate for synaptic input and neural circuit formation. As such, this dissertation supports the hypothesis that neuron type impacts the realization of Dscam function. In fact, in Drosophila motoneurons, Dscam serves a previously unknown cell-autonomous function in dendrite growth. Dscam manipulations produced a range of dendritic phenotypes with alteration in branch number and length. Subsequent experiments exploited the dendritic alterations produced by Dscam manipulations in order to correlate dendritic structure with the suggested function of these neurons. These data indicate that basic motoneuron function and behavior are maintained even in the absence of all adult dendrites within the same neuron. By contrast, dendrites are required for adjusting motoneuron responses to specific challenging behavioral requirements. Here, I establish a direct link between dendritic structure and neuronal function at the level of the single cell, thus defining the structural substrates necessary for conferring various aspects of functional motor output. Taken together, information gathered from these studies can inform the quest in deciphering how complex cell morphologies and networks form and are precisely linked to their function.
ContributorsHutchinson, Katie Marie (Author) / Duch, Carsten (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newfeld, Stuart (Committee member) / Smith, Brian (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2013
Description
Bully victimization has been associated with blunted cardiovascular responses to stress as well as elevated responses to stress. The difference between these altered physiological responses to stress is largely unknown. This study explored several possible moderators to the relationship between chronic stress and future cardiac output (an indicator of increased stress) in response to future stressors. These moderators include the difference between social and physical stressors and individual levels of loneliness. Participants were administered measures of loneliness and victimization history, and led to anticipate either a "social" (recorded speech) or "non-social" (pain tolerance test ) stressor, neither of which occurred. EKG and impedance cardiography were measured throughout the session. When anticipating both stressors, loneliness and victimization were associated with increased CO. A regression revealed a three-way interaction, with change in cardiac output depending on victimization history, loneliness, and condition in the physical stressor condition. Loneliness magnified the CO output levels of non-bullied individuals when facing a physical stressor. These results suggest that non- bullied participants high in loneliness are more stressed out when facing stressors, particularly stressors that are physically threatening in nature.
ContributorsHaneline, Magen (Author) / Newman, Matt (Thesis advisor) / Salerno, Jessica (Committee member) / Miller, Paul (Committee member) / Arizona State University (Publisher)
Created2013
Description
Type 1 Diabetes Mellitus (T1DM) is a chronic disease that requires maintaining tight metabolic control through complex behavioral and pharmaceutical regimens. Subtle cognitive impairments and stress response dysregulation may partially account for problems negotiating life changes and maintaining treatment adherence among emerging adults. The current study examined whether young adults with T1DM physiologically respond to psychological stress in a dysregulated manner compared to non-diabetic peers, and if such individuals also demonstrated greater cognitive declines following psychological stress. Participants included 23 young adults with T1DM and 52 non-diabetic controls yoked to T1DM participants based on age, gender, ethnicity, participant education, and maternal education. Participants completed a laboratory-based social stressor, pre- and post-stressor neurocognitive testing, provided fingerstick blood spots (for glucose levels) and salivary samples (for cortisol levels) at five points across the protocol, and completed psychosocial questionnaires. Related measures ANOVAs were conducted to assess differences between T1DM participants and the average of yoked controls on cortisol and cognitive outcomes. Results demonstrated that differences in cortisol reactivity were dependent on T1DM participants' use of insulin pump therapy (IPT). T1DM participants not using IPT demonstrated elevated cortisol reactivity compared to matched controls. There was no difference in cortisol reactivity between the T1DM participants on IPT and matched controls. On the Stroop task, performance patterns did not differ between participants with T1DM not on IPT and matched controls. The performance of participants with T1DM on IPT slightly improved following the stressor and matched controls slightly worsened. On the Trail Making Test, the performance of participants with T1DM was not different following the stressor whereas participants without T1DM demonstrated a decline following the stressor. Participants with and without T1DM did not differ in patterns of performance on the Rey Verbal Learning Task, Sustained Attention Allocation Task, Controlled Oral Word Association Task, or overall cortisol output across participation. The results of this study are suggestive of an exaggerated cortisol response to psychological stress in T1DM and indicate potential direct and indirect protective influences of IPT.
ContributorsMarreiro, Catherine (Author) / Luecken, Linda (Thesis advisor) / Doane, Leah (Thesis advisor) / Barrera, Manuel (Committee member) / Aiken, Leona (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
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
Learning by trial-and-error requires retrospective information that whether a past action resulted in a rewarded outcome. Previous outcome in turn may provide information to guide future behavioral adjustment. But the specific contribution of this information to learning a task and the neural representations during the trial-and-error learning process is not well understood. In this dissertation, such learning is analyzed by means of single unit neural recordings in the rats' motor agranular medial (AGm) and agranular lateral (AGl) while the rats learned to perform a directional choice task. Multichannel chronic recordings using implanted microelectrodes in the rat's brain were essential to this study. Also for fundamental scientific investigations in general and for some applications such as brain machine interface, the recorded neural waveforms need to be analyzed first to identify neural action potentials as basic computing units. Prior to analyzing and modeling the recorded neural signals, this dissertation proposes an advanced spike sorting system, the M-Sorter, to extract the action potentials from raw neural waveforms. The M-Sorter shows better or comparable performance compared with two other popular spike sorters under automatic mode. With the sorted action potentials in place, neuronal activity in the AGm and AGl areas in rats during learning of a directional choice task is examined. Systematic analyses suggest that rat's neural activity in AGm and AGl was modulated by previous trial outcomes during learning. Single unit based neural dynamics during task learning are described in detail in the dissertation. Furthermore, the differences in neural modulation between fast and slow learning rats were compared. The results show that the level of neural modulation of previous trial outcome is different in fast and slow learning rats which may in turn suggest an important role of previous trial outcome encoding in learning.
ContributorsYuan, Yu'an (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Chae, Junseok (Committee member) / Arizona State University (Publisher)
Created2014
Description
Animals learn to choose a proper action among alternatives according to the circumstance. Through trial-and-error, animals improve their odds by making correct association between their behavioral choices and external stimuli. While there has been an extensive literature on the theory of learning, it is still unclear how individual neurons and a neural network adapt as learning progresses. In this dissertation, single units in the medial and lateral agranular (AGm and AGl) cortices were recorded as rats learned a directional choice task. The task required the rat to make a left/right side lever press if a light cue appeared on the left/right side of the interface panel. Behavior analysis showed that rat's movement parameters during performance of directional choices became stereotyped very quickly (2-3 days) while learning to solve the directional choice problem took weeks to occur. The entire learning process was further broken down to 3 stages, each having similar number of recording sessions (days). Single unit based firing rate analysis revealed that 1) directional rate modulation was observed in both cortices; 2) the averaged mean rate between left and right trials in the neural ensemble each day did not change significantly among the three learning stages; 3) the rate difference between left and right trials of the ensemble did not change significantly either. Besides, for either left or right trials, the trial-to-trial firing variability of single neurons did not change significantly over the three stages. To explore the spatiotemporal neural pattern of the recorded ensemble, support vector machines (SVMs) were constructed each day to decode the direction of choice in single trials. Improved classification accuracy indicated enhanced discriminability between neural patterns of left and right choices as learning progressed. When using a restricted Boltzmann machine (RBM) model to extract features from neural activity patterns, results further supported the idea that neural firing patterns adapted during the three learning stages to facilitate the neural codes of directional choices. Put together, these findings suggest a spatiotemporal neural coding scheme in a rat AGl and AGm neural ensemble that may be responsible for and contributing to learning the directional choice task.
ContributorsMao, Hongwei (Author) / Si, Jennie (Thesis advisor) / Buneo, Christopher (Committee member) / Cao, Yu (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2014
Description
To uncover the neural correlates to go-directed behavior, single unit action potentials are considered fundamental computing units and have been examined by different analytical methodologies under a broad set of hypotheses. Using a behaving rat performing a directional choice learning task, we aim to study changes in rat's cortical neural patterns while he improved his task performance accuracy from chance to 80% or higher. Specifically, simultaneous multi-channel single unit neural recordings from the rat's agranular medial (AGm) and Agranular lateral (AGl) cortices were analyzed using joint peristimulus time histogram (JPSTHs), which effectively unveils firing coincidences in neural action potentials. My results based on data from six rats revealed that coincidences of pair-wise neural action potentials are higher when rats were performing the task than they were not at the learning stage, and this trend abated after the rats learned the task. Another finding is that the coincidences at the learning stage are stronger than that when the rats learned the task especially when they were performing the task. Therefore, this coincidence measure is the highest when the rats were performing the task at the learning stage. This may suggest that neural coincidences play a role in the coordination and communication among populations of neurons engaged in a purposeful act. Additionally, attention and working memory may have contributed to the modulation of neural coincidences during the designed task.
ContributorsCheng, Bing (Author) / Si, Jennie (Thesis advisor) / Chae, Junseok (Committee member) / Seo, Jae-Sun (Committee member) / Arizona State University (Publisher)
Created2014