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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
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

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
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Description
This study examines the effect of exercise therapy on a stationary bike on cognitive function, specifically inhibition and set-switching, in adolescents with Down syndrome. 44 participants were randomly divided between the voluntary cycling therapy group (VCT) (i.e., self-selected cadence), assisted cycling therapy group (ACT) (i.e., 30% faster than self-selected cadence

This study examines the effect of exercise therapy on a stationary bike on cognitive function, specifically inhibition and set-switching, in adolescents with Down syndrome. 44 participants were randomly divided between the voluntary cycling therapy group (VCT) (i.e., self-selected cadence), assisted cycling therapy group (ACT) (i.e., 30% faster than self-selected cadence accomplished by a motor), and a control group (NC) in which the participants did not undergo any exercise therapy. Both cycling groups rode a stationary bicycle, for 30 minutes, three times a week, for eight-weeks. At the beginning (i.e., pretest) and end (i.e., posttest) of the eight-week session the participants completed tasks to evaluate their cognitive function. They completed three trials of the card sort test (i.e., set-switching) and three trials of the knock-tap test (i.e, inhibition) before and after eight-weeks of cycling therapy. The scores of these tests were analyzed using one-way ANOVA between groups and paired samples t-tests. The results showed that after eight-weeks of cycling therapy the participants in the VCT group performed worse in the knock-tap test, but improved in two trials of the card sort test. The results also showed that the participants in the ACT group performed worse after eight-weeks of exercise therapy in one trial of the card sort test. No significant changes were seen for the control group. Due to the fact that on average the participants in the VCT group cycled with a higher heart rate, our results suggest exercise that significantly elevates heart rate can improve cognitive function, specifically set-switching, in adolescents with Down syndrome.
ContributorsBenson, Alicia Meigh (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Maraj, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
This study examines the one month retention of executive function benefits gained by adolescents with Down syndrome after an 8-week aerobic exercise intervention. Sixteen participants were randomly divided between voluntary (VC) (i.e., self-selected cadence) and assisted (AC) (i.e., 30% faster than self-selected cadence accomplished by a motor) cycling groups, with

This study examines the one month retention of executive function benefits gained by adolescents with Down syndrome after an 8-week aerobic exercise intervention. Sixteen participants were randomly divided between voluntary (VC) (i.e., self-selected cadence) and assisted (AC) (i.e., 30% faster than self-selected cadence accomplished by a motor) cycling groups, with one participant used as a control (NC). Both cycling groups rode a stationary bicycle, for 30 minutes, three times a week, for eight weeks. At the beginning (i.e., pretest) and end (posttest) of the 8-week session, three executive functions including: set-switching, inhibition, and cognitive planning, were tested. Approximately one month after the posttest, all participants underwent the cognitive testing again. The results showed that for the AC group cognitive planning improved after eight weeks of assisted cycling and these improvements were maintained after one month of no cycling. However, no significant differences were found between the cycling groups for our measure of inhibition. Set-switching appeared to be improved by both types of exercise, rather than only assisted, but the improvements were not maintained during the one month retention period for either group. Thus, our results suggest that Assisted Cycling causes potentially permanent changes in the brain in regards to cognitive planning.
ContributorsRichter, Madeline B. (Author) / Ringenbach, Shannon (Thesis director) / Amazeen, Eric (Committee member) / Maraj, Brian (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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Description
Persons with Down Syndrome (DS) have been repeatedly shown to have timing deficits, to move slowly, and to not follow metronomes. This timing deficit in persons with DS requires further study because timing is fundamental to movement control. Furthermore, brain imaging studies have proposed a rate effect in which increased

Persons with Down Syndrome (DS) have been repeatedly shown to have timing deficits, to move slowly, and to not follow metronomes. This timing deficit in persons with DS requires further study because timing is fundamental to movement control. Furthermore, brain imaging studies have proposed a rate effect in which increased cortical activation in the primary motor cortex was observed during increased finger movement frequency. The aim of the current study was to determine if the rate effect was present in persons with DS by comparing brain activation in self-selected and as fast as possible rates. Eight participants with DS performed unimanual drumming at their self-selected and maximal rates. Movement rate was measured at EEG was collected in the alpha (8-12 Hz) and Beta (13-30 Hz) frequencies from C3 and C4. The results showed that overall, their self-selected rates were slower than their maximal rates, indicating that they are capable of modifying their movement rate with general instructions. Furthermore, there were significant differences in Beta in which there was more activation during as fast as possible than self-selected tapping in both sides of the primary motor cortex in persons with DS. This suggests that their brains are activated in a similar manner as the typical population with respect to movement rate. Overall, our results suggest that while interventions that involve timing to specific rates are difficult, people with DS can perform at self-selected and maximal rates. The results of our study show that they can alter movement rate when provided with general instruction or additional motivation.
ContributorsCarrington, Elise Almader (Author) / Ringenbach, Shannon (Thesis director) / Crews, Debbie (Committee member) / Hillman, Charles (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-05
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Description
Individuals with Down Syndrome (DS) are subject to a spectrum of behavioral, cognitive and physical impairments. This population is more predisposed to comorbidity and typically has an increased risk of inactivity resulting in a lower level of fitness. Previous studies on physical activity have shown that routine exercise has similar

Individuals with Down Syndrome (DS) are subject to a spectrum of behavioral, cognitive and physical impairments. This population is more predisposed to comorbidity and typically has an increased risk of inactivity resulting in a lower level of fitness. Previous studies on physical activity have shown that routine exercise has similar health benefits for those with DS as those individuals without a disability and in turn progresses their balance ability. Due to limited exercise program opportunities and studies that intentionally investigate the benefits of specific modes of exercise on the DS population, a community-based Exercise Program for Adults with DS (ExDS) was created with the goal of improving their physical and mental health and measuring changes in their balance capabilities throughout the program. ExDS partnered with Arizona State University (ASU) students to create biweekly customized workouts, that followed exercise prescription guidelines, consisting of an aerobic warm-up, main aerobic exercise bout, resistance training, balance training, and stretching for each participant with DS. Participant dynamic and static balance ability was measured using the Berg Balance Scale (BBS) during program pre- and post-assessments. The BBS composite score did not change and no significant improvement was seen in the p-values for each line item of the BBS from pre- to post-testing. For follow-up analyses, the participants with low treatment fidelity were removed. Follow-up analyses showed significant increases in BBS composite score and line item 13 from pre- to post-testing. Treatment fidelity was a limitation in this study and future studies should aim to increase fidelity and consistency of tester for pre- and post-testing. In conclusion, holistic exercise programming for adults with DS appears to benefit balance as long as treatment fidelity is high. It is unclear which mode of exercise had the greatest impact on changes in balance.
ContributorsShikles, Ann Kelly (Author) / Holzapfel, Simon (Thesis director) / Ringenbach, Shannon (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Down Syndrome (DS), caused by the trisomy 21, is the most common intellectual developmental disorder. Children with DS display deficits in ample memory tasks attributed to alterations in memory-related brain structures, including the hippocampus. Although, many studies in DS focused on development of the brain during prenatal stages, little

Down Syndrome (DS), caused by the trisomy 21, is the most common intellectual developmental disorder. Children with DS display deficits in ample memory tasks attributed to alterations in memory-related brain structures, including the hippocampus. Although, many studies in DS focused on development of the brain during prenatal stages, little is known about the cellular evolution of the hippocampus in postnatal periods in DS. Therefore, here we examined the neurochemical spatiotemporal development of neuronal profiles in pediatric postnatal hippocampus in DS and neurotypical developing (NTD) controls. A quantitative and qualitative neuronal distribution was performed in hippocampal sections containing the proper hippocampus, dentate gyrus (DG) and subiculum obtained at autopsy from 1 day to 3 year-old infants in DS and NTD age-matched controls using antibodies against the non-phosphorylated high-molecular-weight neurofilament, a marker of differentiated neurons (SMI-32), the calcium binding protein calbindin D-28k (CAB), and the migration neuronal marker microtubule-associated protein doublecortin (DCX). In addition, Aβ and phosphorylated tau was also immunohistochemically examined in the hippocampus using 6E10, Aβ1-42 and the phosphorylated CP-13 and AT8 tau antibodies, respectively. We found APP/Aβ immunoreactivity, but not Aβ1-42, in diffuse-like plaques in the hippocampus from 1 day to 3 year old infants and young children in DS and NTD cases. By contrast, phosphorylated fetal tau was not immunodetected in the hippocampus at any age in both groups. SMI-32 immunolabeled neurons were observed in the hilus, CA2 field and subiculum in early postnatal cases in DS and NTD. The number of SMI-32 immunoreactive (ir) granule cells in the DG were significantly decreased in DS compared to NTD. While a strong DCX immunoreactivity was observed in the granule cells of the DG in the hippocampus in both groups at early postnatal stages, a more accelerated reduction was observed in DS. CAB-ir neuronal distribution in the postnatal hippocampus was comparable between the youngest and the oldest infants in NTD and DS. In addition, strong positive correlations were observed between DG-DCX-ir cells numbers and both DG-CAB-ir and DG-SMI-32-ir values as well as negative correlations between the brain weight and DG granule cell-ir numbers for all markers in DS. These findings suggest that neuronal maturation and migration in the hippocampus are compromised in early postnatal stages of the development in DS and may contribute to the intellectual disabilities observed in this group.
ContributorsMoreno, David (Co-author) / Perez, Sylvia E. (Co-author, Thesis director) / Velazquez, Ramon (Thesis director) / Schafernak, Kristian T. (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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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

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