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- Creators: Arizona State University
- Member of: Theses and Dissertations
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
The benefits of exercise have been recommended in typical and other special populations. However, the evidence for persons with Down syndrome (DS) is still limited. This study was aimed at investigating the impact of an acute bout of aerobic exercise intervention on motor performance, executive function and intrinsic motivation in adolescents and young adults with DS. Ten participants with DS were assigned to an exercise group, who walked on a incremental treadmill protocol for 20 minutes. The exercise intensity was achieved at 66% of their predicted maximum heart rate. Another ten participants with DS were assigned to an attentional control group, who watched a video for 20 minutes. Measures of fine manual dexterity (e.g., Purdue Pegboard test), manual force production (e.g., grip strength test), processing speed (e.g., visual choice reaction time test), verbal processing (e.g., verbal fluency test), attention shifting ability (e.g., The Dimensional Card sorting test), and inhibitory control (e.g., Knock and Tap test) were tested pre and post intervention. An intrinsic motivation scale (e.g., enjoyment and effort) was conducted after the intervention. First, results showed participants significantly improved their performance in manual force production and Knock and Tap Test after the exercise intervention. While it has been proposed that exercise increases arousal status, neurotransmitters, or cerebral vasculature, the exact mechanisms in persons with DS are still unknown. However, our results showed that after treadmill walking, motor and cognitive improvements can be found in individuals with DS, even in a single exercise session. In addition, participants reported higher scores in enjoyment after video viewing than exercise, which may a result from musical effect or too much emphasis on external rewards in their early participation in exercise. These may imply that participants had low intrinsic motivation to an active lifestyle. Further, scores in effort were significantly higher after exercise than video viewing, which indicated their capabilities to perceive their physical exertion. However, other motivational regulations (e.g., introjected and identified regulations) have shown the relationship with exercise behavior in this population. Thus, further study should consider divergent motivational factors in order to implement an effective exercise program.
ContributorsChen, Chih-Chia (Author) / Ringenbach, Shannon D.R. (Thesis advisor) / Crews, Debra (Committee member) / Kulinna, Pamela (Committee member) / Amazeen, Eric (Committee member) / Arizona State University (Publisher)
Created2013
Description
Following a traumatic brain injury (TBI) 5-50% of patients will develop post traumatic epilepsy (PTE). Pediatric patients are most susceptible with the highest incidence of PTE. Currently, we cannot prevent the development of PTE and knowledge of basic mechanisms are unknown. This has led to several shortcomings to the treatment of PTE, one of which is the use of anticonvulsant medication to the population of TBI patients that are not likely to develop PTE. The complication of identifying the two populations has been hindered by the ability to find a marker to the pathogenesis of PTE. The central hypothesis of this dissertation is that following TBI, the cortex undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes seizure development. Chapter 2 of this dissertation details excitatory and inhibitory changes in the rat cortex after severe TBI. This dissertation aims to identify cortical changes to a single cell level after severe TBI using whole cell patch clamp and electroencephalogram electrophysiology. The work of this dissertation concluded that excitatory and inhibitory synaptic activity in cortical controlled impact (CCI) animals showed the development of distinct burst discharges that were not present in control animals. The results suggest that CCI induces early "silent" seizures that are detectable on EEG and correlate with changes to the synaptic excitability in the cortex. The synaptic changes and development of burst discharges may play an important role in synchronizing the network and promoting the development of PTE.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2014
Description
Smoking remains the leading cause of preventable death in the United States, and early initiation is associated with greater difficulty quitting. Among adolescent smokers, those with attention-deficit hyperactivity disorder (ADHD), characterized by difficulties associated with impulsivity, hyperactivity, and inattention, smoke at nearly twice the rate of their peers. Although cigarette smoking is highly addictive, nicotine is a relatively weak primary reinforcer, spurring research on other potential targets that may maintain smoking, including the potential benefits of nicotine on attention, inhibition, and reinforcer efficacy. The present study employs the most prevalent rodent model of ADHD, the spontaneously hypertensive rat (SHR) and its control comparison Wistar Kyoto (WKY) to examine the effects of acute and chronic subcutaneous nicotine injections on performance in three operant response inhibition paradigms. Functional activation in select regions of the prefrontal cortex and striatum was also explored. Acute (0.1, 0.3, 0.6 mg/kg) and chronic (0.3 mg/kg) nicotine increased impulsive responding regardless of strain, dose, or operant schedule. Dose-dependent decreases in latency to initiate the task were also observed. SHR receiving daily nicotine injections showed less activation in the nucleus accumbens shell compared to saline controls. Despite close similarities, one of the three operant tasks did not detect response inhibition deficits in SHR relative to WKY. A closer examination of these tasks may highlight critical components involved in the amelioration of response inhibition deficits.
ContributorsMazur, Gabriel Joseph (Author) / Sanabria, Federico (Thesis advisor) / Killeen, Peter R (Committee member) / Neisewander, Janet L (Committee member) / Wynne, Clive DL (Committee member) / Arizona State University (Publisher)
Created2014
Description
The failure to withhold inappropriate behavior is a central component of most impulse control disorders, including Attention Deficit Hyperactivity Disorder (ADHD). The present study examined the effects of housing environment and methylphenidate (a drug often prescribed for ADHD) on the performance of rats in two response inhibition tasks: differential reinforcement of low rate (DRL) and fixed minimum interval (FMI). Both tasks required rats to wait a fixed amount of time (6 s) before emitting a reinforced response. The capacity to withhold the target response (volitional inhibition) and timing precision were estimated on the basis of performance in each of the tasks. Paradoxically, rats housed in a mildly enriched environment that included a conspecific displayed less volitional inhibition in both tasks compared to rats housed in an isolated environment. Enriched housing, however, increased timing precision. Acute administration of methylphenidate partially reversed the effects of enriched housing. Implications of these results in the assessment and treatment of ADHD-related impulsivity are discussed.
ContributorsHill, Jade C (Author) / Sanabria, Federico (Thesis advisor) / Killeen, Peter (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2011
Description
Dopamine (DA) is a neurotransmitter involved in attention, goal oriented behavior, movement, reward learning, and short term and working memory. For the past four decades, mathematical and computational modeling approaches have been useful in DA research, and although every modeling approach has limitations, a model is an efficient way to generate and explore hypotheses. This work develops a model of DA dynamics in a representative, single DA neuron by integrating previous experimental, theoretical and computational research. The model consists of three compartments: the cytosol, the vesicles, and the extracellular space and forms the basis of a new mathematical paradigm for examining the dynamics of DA synthesis, storage, release and reuptake. The model can be driven by action potentials generated by any model of excitable membrane potential or even from experimentally induced depolarization voltage recordings. Here the model is forced by a previously published model of the excitable membrane of a mesencephalic DA neuron in order to study the biochemical processes involved in extracellular DA production. After demonstrating that the model exhibits realistic dynamics resembling those observed experimentally, the model is used to examine the functional changes in presynaptic mechanisms due to application of cocaine. Sensitivity analysis and numerical studies that focus on various possible mechanisms for the inhibition of DAT by cocaine provide insight for the complex interactions involved in DA dynamics. In particular, comparing numerical results for a mixed inhibition mechanism to those for competitive, non-competitive and uncompetitive inhibition mechanisms reveals many behavioral similarities for these different types of inhibition that depend on inhibition parameters and levels of cocaine. Placing experimental results within this context of mixed inhibition provides a possible explanation for the conflicting views of uptake inhibition mechanisms found in experimental neuroscience literature.
ContributorsTello-Bravo, David (Author) / Crook, Sharon M (Thesis advisor) / Greenwood, Priscilla E (Thesis advisor) / Baer, Steven M. (Committee member) / Castaneda, Edward (Committee member) / Castillo-Chavez, Carlos (Committee member) / Arizona State University (Publisher)
Created2012
Description
The purpose of this study, originally, was to contribute to the completion of a meta-analysis conducted by Mara Wierstra from the University of Virginia. Wierstra had requested individual participant data from two separate studies conducted in our lab: "Acute bouts of assisted cycling improves cognitive and upper extremity movement functions in adolescents with Down syndrome" and "Assisted Cycling Therapy (ACT) improves inhibition in adolescents with autism spectrum disorder." From the data requested, the participants were required to complete three separate tests (i.e., Tower of London, Trail Making Task and the Stroop Test). After compiling the data and sending it to her, we decided to conduct a small meta-analysis of our own, drawing connecting conclusions from the data from the two studies. We concluded that observationally our data suggest an advantage for ACT over voluntary cycling and no cycling across two separate populations (i.e., Autism Spectrum Disorder and Down syndrome), and across different measures of executive function (i.e., Stroop Test, Trail Making Test, and Tower of London). The data suggest that the ACT interventions may promote the upregulation of neurotropic factors leading to neurogenesis in the prefrontal cortex of the brain.
ContributorsParker, Cade Joseph (Author) / Ringenbach, Shannon (Thesis director) / Holzapfel, Simon (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
In this study, the oppositional processes theory was proposed to suggest that reliance on semantic and episodic memory systems hinder originality during idea generation for divergent thinking tasks that are generally used to assess creative potential. In order to investigate the proposed oppositional processes theory, three experiments that manipulated the memory accessibility in participants during the alternative uses tasks were conducted. Experiment 1 directly instructed participants to either generate usages based on memory or not from memory; Experiment 2 provided participants with object cues that were either very common or very rare in daily life (i.e., bottle vs. canteen); Experiment 3 replicated the same manipulation from Experiment 2 with much longer generation time (10 minutes in Experiment 2 vs. 30 minutes in Experiment 3). The oppositional processes theory predicted that participants who had less access to direct and unaltered usages (i.e., told to not use memory, were given rare cues, or were outputting items later in the generation period) during the task would be more creative. Results generally supported the predictions in Experiments 1 and 2 where participants from conditions which limited their access to memory generated more novel usages that were considered more creative by independent coders. Such effects were less prominent in Experiment 3 with extended generation time but the trends remained the same.
ContributorsXu, Dongchen (Author) / Brewer, Gene (Thesis advisor) / Glenberg, Arthur (Committee member) / Homa, Donald (Committee member) / Goldinger, Stephen (Committee member) / Arizona State University (Publisher)
Created2017
Description
It has been suggested that directed forgetting (DF) in the item-method paradigm results from selective rehearsal of R items and passive decay of F items. However, recent evidence suggested that the passive decay explanation is insufficient. The current experiments examined two theories of DF that assume an active forgetting process: (1) attentional inhibition and (2) tagging and selective search (TSS). Across three experiments, the central tenets of these theories were evaluated. Experiment 1 included encoding manipulations in an attempt to distinguish between these competing theories, but the results were inconclusive. Experiments 2 and 3 examined the theories separately. The results from Experiment 2 supported a representation suppression account of attentional inhibition, while the evidence from Experiment 3 suggested that TSS was not a viable mechanism for DF. Overall, the results provide additional evidence that forgetting is due to an active process, and suggest this process may act to suppress the representations of F items.
ContributorsHansen, Whitney Anne (Author) / Goldinger, Stephen D. (Thesis advisor) / Azuma, Tamiko (Committee member) / Brewer, Gene (Committee member) / Homa, Donald (Committee member) / Arizona State University (Publisher)
Created2011
Description
Background: Down syndrome is the leading genetic cause of intellectual disabilities. Executive function is an area that people with Down syndrome have a diminished capacity compared to those in the general population. In recent years it has been determined that acute and chronic exercise has a small but positive effect on measures of executive function in typically developed individuals. The effect has been recorded separately in both aerobic, high-rate passive and resistance exercises in adolescents with DS but has not been compared between exercise types in adults with DS. Methods: A randomized crossover study was utilized to determine the effect of resistance exercise, assisted cycling therapy, and no exercise on executive function and enjoyment in adults with Down syndrome. Resistance Training (RT)- participants completed a total of 16- repetitions of approximately 75% of a 1-RM in the leg press, chest press, seated row, and latissimus pulldown. ACT- participants completed 30-minutes of cycling at 35% above voluntary (e.g., self-selected pace) rate. No-Training (NT)- participants spent 35-minutes playing board games. Cognitive assessments were recorded pre- and post- intervention. The Physical Activity Enjoyment Survey was collected post-intervention. Statistics: The cognitive measures and Physical Activity Self-efficacy scale were analyzed using the delta scores (pre-post) in a Linear mixed models analyais. The main effect of sequence (A, B, C) and intervention (RT, ACT, NT), and visit were assessed. Significance level was set with α=0.05. If any differences were detected, the Bonferroni post-hoc test was used to determine differences. Physical Activity Enjoyment Scale post scores were compared using a General Linear Model. Alpha was set at 0.05 with a Bonferroni post-hoc test to determine differences. A secondary analysis was conducted investigating the effect of participants that completed testing individually compared to those that completed the testing in a group setting. Results: There were no significant difference in the delta score of any of the measures. The secondary analysis also found no significant difference but showed a trend that those tested individually had opposite results than those tested in a group.
ContributorsArnold, Nathaniel (Author) / Ringenbach, Shannon (Thesis advisor) / Lee, Chong (Committee member) / Der Ananian, Cheryl (Committee member) / Holzapfel, Simon (Committee member) / Bosch, Pamela (Committee member) / Arizona State University (Publisher)
Created2021