Matching Items (4)
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- All Subjects: Drosophila
- All Subjects: Fluid Intelligence
- Creators: Duch, Carsten
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
Previous research has yielded an equivocal answer as to whether speaking aloud while performing intelligence tasks improves, impairs, or has no effect on performance. Some studies show that it impairs performance while others show it aids performance. In the studies in which speaking aloud has been shown to help, only children and older adults benefitted. The present study investigated whether college-aged students benefit from speaking aloud while performing a fluid intelligence test. Subjects performed a battery of working memory and intelligence tasks silently. Once they had completed each task, the participants took them again, though this time they spoke aloud while completing the tests. Results showed that subjects did insignificantly worse on the working memory tests when speaking aloud. However, subjects performed significantly better on the measures of fluid intelligence while speaking aloud as opposed to doing them silently. At an individual differences level, low working memory capacity participants benefited more from speaking aloud than the high working memory ones. Finally, we found a positive correlation between working memory scores and fluid intelligence scores, offering further evidence that the two constructs are related, yet different.
ContributorsRice, Z. Douglas (Author) / Brewer, Gene (Thesis director) / Duch, Carsten (Committee member) / Ball, Hunter (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Working memory capacity and fluid intelligence are important predictors of performance in educational settings. Thus, understanding the processes underlying the relation between working memory capacity and fluid intelligence is important. Three large scale individual differences experiments were conducted to determine the mechanisms underlying the relation between working memory capacity and fluid intelligence. Experiments 1 and 2 were designed to assess whether individual differences in strategic behavior contribute to the variance shared between working memory capacity and fluid intelligence. In Experiment 3, competing theories for describing the underlying processes (cognitive vs. strategy) were evaluated in a comprehensive examination of potential underlying mechanisms. These data help inform existing theories about the mechanisms underlying the relation between WMC and gF. However, these data also indicate that the current theoretical model of the shared variance between WMC and gF would need to be revised to account for the data in Experiment 3. Possible sources of misfit are considered in the discussion along with a consideration of the theoretical implications of observing those relations in the Experiment 3 data.
ContributorsWingert, Kimberly Marie (Author) / Brewer, Gene A. (Thesis advisor) / McNamara, Danielle (Thesis advisor) / McClure, Samuel (Committee member) / Redick, Thomas (Committee member) / Arizona State University (Publisher)
Created2018
Description
Methyl-CpG binding protein 2 (MECP2) is a widely abundant, multifunctional regulator of gene expression with highest levels of expression in mature neurons. In humans, both loss- and gain-of-function mutations of MECP2 cause mental retardation and motor dysfunction classified as either Rett Syndrome (RTT, loss-of-function) or MECP2 Duplication Syndrome (MDS, gain-of-function). At the cellular level, MECP2 mutations cause both synaptic and dendritic defects. Despite identification of MECP2 as a cause for RTT nearly 16 years ago, little progress has been made in identifying effective treatments. Investigating major cellular and molecular targets of MECP2 in model systems can help elucidate how mutation of this single gene leads to nervous system and behavioral defects, which can ultimately lead to novel therapeutic strategies for RTT and MDS. In the work presented here, I use the fruit fly, Drosophila melanogaster, as a model system to study specific cellular and molecular functions of MECP2 in neurons. First, I show that targeted expression of human MECP2 in Drosophila flight motoneurons causes impaired dendritic growth and flight behavioral performance. These effects are not caused by a general toxic effect of MECP2 overexpression in Drosophila neurons, but are critically dependent on the methyl-binding domain of MECP2. This study shows for the first time cellular consequences of MECP2 gain-of-function in Drosophila neurons. Second, I use RNA-Seq to identify KIBRA, a gene associated with learning and memory in humans, as a novel target of MECP2 involved in the dendritic growth phenotype. I confirm bidirectional regulation of Kibra by Mecp2 in mouse, highlighting the translational utility of the Drosophila model. Finally, I use this system to identify a novel role for the C-terminus in regulating the function of MECP in apoptosis and verify this finding in mammalian cell culture. In summary, this work has established Drosophila as a translational model to study the cellular effects of MECP2 gain-of-function in neurons, and provides insight into the function of MECP2 in dendritic growth and apoptosis.
ContributorsWilliams, Alison (Author) / Duch, Carsten (Thesis advisor) / Orchinik, Miles (Committee member) / Gallitano, Amelia (Committee member) / Huentelman, Matthew (Committee member) / Narayanan, Vinodh (Committee member) / Newfeld, Stuart (Committee member) / Arizona State University (Publisher)
Created2015