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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

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
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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

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
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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

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
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Description
The aim of this study is to examine the relationship between Assisted Cycle Therapy, leisure time activity levels, fine motor control, and grip force in older adults with Down syndrome (DS), all of which affect activities of daily living (ADL) and therefore quality of life. This is relevant because this

The aim of this study is to examine the relationship between Assisted Cycle Therapy, leisure time activity levels, fine motor control, and grip force in older adults with Down syndrome (DS), all of which affect activities of daily living (ADL) and therefore quality of life. This is relevant because this particular group is at risk for developing early onset Alzheimer's disease (AD), which presents itself uniquely in this population. The parent or guardian of six participants with DS completed Godin's Leisure Time Exercise Questionnaire and the participants themselves completed Purdue Pegboard and grip force assessments before and after an 8-week exercise intervention. The results were inconsistent with past research, with no change being seen in fine motor control or grip force and a decrease being seen in leisure activity. These findings are indicative of the importance of the effect of fatigue on leisure activity as well as maintaining elevated heart rate throughout exercise interventions.
ContributorsGomez, Elizabeth Danielle (Author) / Ringenbach, Shannon (Thesis director) / Coon, David (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor)
Created2015-05
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Description
The purpose of the study was to examine the effectiveness of two modes of exercise on depression in adolescents with Down syndrome (DS). Twelve participants randomly completed one of two exercise interventions. The interventions were: 1) Voluntary Cycling (VC), in which participants cycled at their self-selected pedaling rate 2) Assisted

The purpose of the study was to examine the effectiveness of two modes of exercise on depression in adolescents with Down syndrome (DS). Twelve participants randomly completed one of two exercise interventions. The interventions were: 1) Voluntary Cycling (VC), in which participants cycled at their self-selected pedaling rate 2) Assisted Cycling (AC), in which the participants' voluntary pedaling rates were augmented with a motor to ensure the maintenance of 80 rpms. In each intervention, the participant completed three cycling sessions each week for a total of eight weeks. Depression scores did decrease or improved after both AC and VC, but not significantly. There was a greater mean improvement for participants in the AC group than VC when analyzing total score and t-score. Future research will include a greater sample size and control group to reach significant results as well as try and reveal the mechanisms involved in these mental health improvements found after an acute bout of assisted cycling in adolescents with DS.
ContributorsTeslevich, Jennifer Lynn (Author) / Ringenbach, Shannon (Thesis director) / Kulinna, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / Department of Psychology (Contributor)
Created2013-12
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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

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
Statistics show that the termination rates for fetuses with Down syndrome are substantially higher compared to the general population. Perhaps pregnant women are led to believe that this is the best option for them. The information that leads them to this conclusion could be one of the leading factors for

Statistics show that the termination rates for fetuses with Down syndrome are substantially higher compared to the general population. Perhaps pregnant women are led to believe that this is the best option for them. The information that leads them to this conclusion could be one of the leading factors for the high termination rates. In an attempt to understand the reasons behind the high termination rates the following question must be addressed: “What information is available to pregnant women that may influence their decision to terminate or not terminate fetuses with Trisomy 21?” In order to answer this question I completed a comprehensive literature review of the information available to pregnant women in the United States after they find out there fetus has Trisomy 21. The results showed that many sources publish information that is straightforward, factual, and attempts to make sure that pregnant women are fully informed on the reality of life with a child with Down syndrome. However, there are also many sources that publish information that is biased and attempts to influence a woman’s decision of whether to keep or abort her fetus with Trisomy 21. The results from this study suggest that the message conveyed from a given article relies heavily on who is doing the writing, the type of article it is, and were it is published. This provides women with a confusing array of different ideas, as opposed to offering them objective facts and consistent information. When a pregnant woman is told that her fetus is positive for the Trisomy 21 disorder and will be born with Down syndrome, it can be a very scary and emotional time. Women in this situation deserve easy access the correct information in order to help them make an informed decision based on their own choice and not the opinion of someone else.
ContributorsFitzgerald, Grace (Author) / Maienschein, Jane (Thesis director) / Ziganshina, Dina (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Molecular Sciences (Contributor)
Created2022-05
Description
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. When TBI occurs in children it often results in severe cognitive and behavioral deficits. Post-injury, the pediatric brain may be sensitive to the effects of TBI while undergoing a number of age-dependent physiological

Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. When TBI occurs in children it often results in severe cognitive and behavioral deficits. Post-injury, the pediatric brain may be sensitive to the effects of TBI while undergoing a number of age-dependent physiological and neurobiological changes. Due to the nature of the developing cortex, it is important to understand how a pediatric brain recovers from a severe TBI (sTBI) compared to an adult. Investigating major cortical and cellular changes after sTBI in a pediatric model can elucidate why pediatrics go on to suffer more neurological damage than an adult after head trauma. To model pediatric sTBI, I use controlled cortical impact (CCI) in juvenile mice (P22). First, I show that by 14 days after injury, animals begin to show recurrent, non-injury induced, electrographic seizures. Also, using whole-cell patch clamp, layer V pyramidal neurons in the peri-injury area show no changes except single-cell excitatory and inhibitory synaptic bursts. These results demonstrate that CCI induces epileptiform activity and distinct synaptic bursting within 14 days of injury without altering the intrinsic properties of layer V pyramidal neurons. Second, I characterized changes to the cortical inhibitory network and how fast-spiking (FS) interneurons in the peri-injury region function after CCI. I found that there is no loss of interneurons in the injury zone, but a 70% loss of parvalbumin immunoreactivity (PV-IR). FS neurons received less inhibitory input and greater excitatory input. Finally, I show that the cortical interneuron network is also affected in the contralateral motor cortex. The contralateral motor cortex shows a loss of interneurons and loss of PV-IR. Contralateral FS neurons in the motor cortex synaptically showed greater excitatory input and less inhibitory input 14 days after injury. In summary, this work demonstrates that by 14 days after injury, the pediatric cortex develops epileptiform activity likely due to cortical inhibitory network dysfunction. These findings provide novel insight into how pediatric cortical networks function in the injured brain and suggest potential circuit level mechanisms that may contribute to neurological disorders as a result of TBI.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Newbern, Jason (Thesis advisor) / Neisewander, Janet (Committee member) / Qiu, Shenfeng (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2015
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Description

Statistics show that the termination rates for fetuses with Down syndrome are substantially higher compared to the general population. Perhaps pregnant women are led to believe that this is the best option for them. The information that leads them to this conclusion could be one of the leading factors for

Statistics show that the termination rates for fetuses with Down syndrome are substantially higher compared to the general population. Perhaps pregnant women are led to believe that this is the best option for them. The information that leads them to this conclusion could be one of the leading factors for the high termination rates. In an attempt to understand the reasons behind the high termination rates the following question must be addressed: “What information is available to pregnant women that may influence their decision to terminate or not terminate fetuses with Trisomy 21?” In order to answer this question I completed a comprehensive literature review of the information available to pregnant women in the United States after they find out there fetus has Trisomy 21. The results showed that many sources publish information that is straightforward, factual, and attempts to make sure that pregnant women are fully informed on the reality of life with a child with Down syndrome. However, there are also many sources that publish information that is biased and attempts to influence a woman’s decision of whether to keep or abort her fetus with Trisomy 21. The results from this study suggest that the message conveyed from a given article relies heavily on who is doing the writing, the type of article it is, and were it is published. This provides women with a confusing array of different ideas, as opposed to offering them objective facts and consistent information. When a pregnant woman is told that her fetus is positive for the Trisomy 21 disorder and will be born with Down syndrome, it can be a very scary and emotional time. Women in this situation deserve easy access the correct information in order to help them make an informed decision based on their own choice and not the opinion of someone else.

ContributorsFitzgerald, Grace (Author) / Maienschein, Jane (Thesis director) / Ziganshina, Dina (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2022-05
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Description

Statistics show that the termination rates for fetuses with Down syndrome are substantially higher compared to the general population. Perhaps pregnant women are led to believe that this is the best option for them. The information that leads them to this conclusion could be one of the leading factors for

Statistics show that the termination rates for fetuses with Down syndrome are substantially higher compared to the general population. Perhaps pregnant women are led to believe that this is the best option for them. The information that leads them to this conclusion could be one of the leading factors for the high termination rates. In an attempt to understand the reasons behind the high termination rates the following question must be addressed: “What information is available to pregnant women that may influence their decision to terminate or not terminate fetuses with Trisomy 21?” In order to answer this question I completed a comprehensive literature review of the information available to pregnant women in the United States after they find out there fetus has Trisomy 21. The results showed that many sources publish information that is straightforward, factual, and attempts to make sure that pregnant women are fully informed on the reality of life with a child with Down syndrome. However, there are also many sources that publish information that is biased and attempts to influence a woman’s decision of whether to keep or abort her fetus with Trisomy 21. The results from this study suggest that the message conveyed from a given article relies heavily on who is doing the writing, the type of article it is, and were it is published. This provides women with a confusing array of different ideas, as opposed to offering them objective facts and consistent information. When a pregnant woman is told that her fetus is positive for the Trisomy 21 disorder and will be born with Down syndrome, it can be a very scary and emotional time. Women in this situation deserve easy access the correct information in order to help them make an informed decision based on their own choice and not the opinion of someone else.

ContributorsFitzgerald, Grace (Author) / Maienschein, Jane (Thesis director) / Ziganshina, Dina (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2022-05