Matching Items (29)
Filtering by
- Language: English
Description
Olfaction is an important sensory modality for behavior since odors inform animals of the presence of food, potential mates, and predators. The fruit fly, Drosophila melanogaster, is a favorable model organism for the investigation of the biophysical mechanisms that contribute to olfaction because its olfactory system is anatomically similar to but simpler than that of vertebrates. In the Drosophila olfactory system, sensory transduction takes place in olfactory receptor neurons housed in the antennae and maxillary palps on the front of the head. The first stage of olfactory processing resides in the antennal lobe, where the structural unit is the glomerulus. There are at least three classes of neurons in the antennal lobe - excitatory projection neurons, excitatory local neurons, and inhibitory local neurons. The arborizations of the local neurons are confined to the antennal lobe, and output from the antennal lobe is carried by projection neurons to higher regions of the brain. Different views exist of how circuits of the Drosophila antennal lobe translate input from the olfactory receptor neurons into projection neuron output. We construct a conductance based neuronal network model of the Drosophila antennal lobe with the aim of understanding possible mechanisms within the antennal lobe that account for the variety of projection neuron activity observed in experimental data. We explore possible outputs obtained from olfactory receptor neuron input that mimic experimental recordings under different connectivity paradigms. First, we develop realistic minimal cell models for the excitatory local neurons, inhibitory local neurons, and projections neurons based on experimental data for Drosophila channel kinetics, and explore the firing characteristics and mathematical structure of these models. We then investigate possible interglomerular and intraglomerular connectivity patterns in the Drosophila antennal lobe, where olfactory receptor neuron input to the antennal lobe is modeled with Poisson spike trains, and synaptic connections within the antennal lobe are mediated by chemical synapses and gap junctions as described in the Drosophila antennal lobe literature. Our simulation results show that inhibitory local neurons spread inhibition among all glomeruli, where projection neuron responses are decreased relatively uniformly for connections of synaptic strengths that are homogeneous. Also, in the case of homogeneous excitatory synaptic connections, the excitatory local neuron network facilitates odor detection in the presence of weak stimuli. Excitatory local neurons can spread excitation from projection neurons that receive more input from olfactory receptor neurons to projection neurons that receive less input from olfactory receptor neurons. For the parameter values for the network models associated with these results, eLNs decrease the ability of the network to discriminate among single odors.
ContributorsLuli, Dori (Author) / Crook, Sharon (Thesis advisor) / Baer, Steven (Committee member) / Castillo-Chavez, Carlos (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2013
Description
A general continuum model for simulating the flow of ions in the salt baths that surround and fill excitable neurons is developed and presented. The ion densities and electric potential are computed using the drift-diffusion equations. In addition, a detailed model is given for handling the electrical dynamics on interior membrane boundaries, including a model for ion channels in the membranes that facilitate the transfer of ions in and out of cells. The model is applied to the triad synapse found in the outer plexiform layer of the retina in most species. Experimental evidence suggests the existence of a negative feedback pathway between horizontal cells and cone photoreceptors that modulates the flow of calcium ions into the synaptic terminals of cones. However, the underlying mechanism for this feedback is controversial and there are currently three competing hypotheses: the ephaptic hypothesis, the pH hypothesis and the GABA hypothesis. The goal of this work is to test some features of the ephaptic hypothesis using detailed simulations that employ rigorous numerical methods. The model is first applied in a simple rectangular geometry to demonstrate the effects of feedback for different extracellular gap widths. The model is then applied to a more complex and realistic geometry to demonstrate the existence of strictly electrical feedback, as predicted by the ephaptic hypothesis. Lastly, the effects of electrical feedback in regards to the behavior of the bipolar cell membrane potential is explored. Figures for the ion densities and electric potential are presented to verify key features of the model. The computed steady state IV curves for several cases are presented, which can be compared to experimental data. The results provide convincing evidence in favor of the ephaptic hypothesis since the existence of feedback that is strictly electrical in nature is shown, without any dependence on pH effects or chemical transmitters.
ContributorsJones, Jeremiah (Author) / Gardner, Carl (Committee member) / Baer, Steven (Committee member) / Crook, Sharon (Committee member) / Kostelich, Eric (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2013
Description
Dendrites are the structures of a neuron specialized to receive input signals and to provide the substrate for the formation of synaptic contacts with other cells. The goal of this work is to study the activity-dependent mechanisms underlying dendritic growth in a single-cell model. For this, the individually identifiable adult motoneuron, MN5, in Drosophila melanogaster was used. This dissertation presents the following results. First, the natural variability of morphological parameters of the MN5 dendritic tree in control flies is not larger than 15%, making MN5 a suitable model for quantitative morphological analysis. Second, three-dimensional topological analyses reveals that different parts of the MN5 dendritic tree innervate spatially separated areas (termed "isoneuronal tiling"). Third, genetic manipulation of the MN5 excitability reveals that both increased and decreased activity lead to dendritic overgrowth; whereas decreased excitability promoted branch elongation, increased excitability enhanced dendritic branching. Next, testing the activity-regulated transcription factor AP-1 for its role in MN5 dendritic development reveals that neural activity enhanced AP-1 transcriptional activity, and that AP-1 expression lead to opposite dendrite fates depending on its expression timing during development. Whereas overexpression of AP-1 at early stages results in loss of dendrites, AP-1 overexpression after the expression of acetylcholine receptors and the formation of all primary dendrites in MN5 causes overgrowth. Fourth, MN5 has been used to examine dendritic development resulting from the expression of the human gene MeCP2, a transcriptional regulator involved in the neurodevelopmental disease Rett syndrome. Targeted expression of full-length human MeCP2 in MN5 causes impaired dendritic growth, showing for the first time the cellular consequences of MeCP2 expression in Drosophila neurons. This dendritic phenotype requires the methyl-binding domain of MeCP2 and the chromatin remodeling protein Osa. In summary, this work has fully established MN5 as a single-neuron model to study mechanisms underlying dendrite development, maintenance and degeneration, and to test the behavioral consequences resulting from dendritic growth misregulation. Furthermore, this thesis provides quantitative description of isoneuronal tiling of a central neuron, offers novel insight into activity- and AP-1 dependent developmental plasticity, and finally, it establishes Drosophila MN5 as a model to study some specific aspects of human diseases.
ContributorsVonhoff, Fernando Jaime (Author) / Duch, Carsten J (Thesis advisor) / Smith, Brian H. (Committee member) / Vu, Eric (Committee member) / Crook, Sharon (Committee member) / Arizona State University (Publisher)
Created2012
Description
Tremendous phenotypic variation exists across people with Turner syndrome (45,X). This variation likely stems from differential dosage of genes on the X chromosome. X-inactivation is the process whereby all X chromosomes in excess of one are silenced. However, about 15% of the genes on the silenced X chromosome escape this inactivation and are candidates for affecting phenotype in people with Turner syndrome. In this study we take an evolutionary approach to rank candidate genes that may contribute to phenotypic variation among people with Turner Syndrome. We incorporate analysis of patterns of DNA methylation from 46,XX and 45,X individuals, and estimates of variable X-inactivation status across 46,XX individuals, with patterns of gene expression conservation on the X chromosomes across five tissues and ten species. We find that genes that escape XCI are possible candidate genes for Turner syndrome phenotype, indicated by the constant levels of expression in escape genes and inactivated genes. Variation in these genes is expected to affect phenotype when dosage is altered from typical levels.
ContributorsSchaffer, Kara Nina (Author) / Wilson Sayres, Melissa (Thesis director) / Crook, Sharon (Committee member) / Narang, Pooja (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Electrical stimulation can be used to activate peripheral nerve fibers to restore sensation to individuals with amputation and the technique is also being investigated as a means of treating a wide range of diseases. Longitudinal intrafascicular electrodes (LIFEs) are one of several types of electrodes that have been used to activate peripheral nerves. LIFEs can be used to activate small groups of fibers within a peripheral nerve fascicle, but the degree of their selectivity is uncertain. To investigate the effects of intrafascicular stimulation on nerve fiber activation, a mathematical, conductance-based model of an axon drawn from the literature was implemented and used to simulate the firing response of sensory nerve fibers in the presence of an applied monopolar electric field. Several axons were simulated to represent axons of different size, conductivity, spatial composition and location with respect to the electrode. Electric field profiles produced by pulses of different pulse widths and pulse amplitudes were created. Each fiber was placed within each resulting electric field and the firing threshold was determined. The effects of changes in pulse width, pulse amplitude, and distance on firing patterns were shown; all of these results were consistent with published experimental findings. The models showed lower firing threshold for smaller fibers than larger fibers and for fibers that were farther from the stimulating electrode than those that were closer. Firing threshold was also lower for stimuli of greater pulse width. Analysis of axon recruitment upon increases in pulse amplitude showed that the effects of fiber distance may be more pronounced than the effects of fiber size. This model can serve as a basis for further development to more accurately represent the effects of LIFEs and eventually may assist in the design of stimulation paradigms and waveforms to improve selectivity of axon activation when using LIFEs.
ContributorsSira, Alarmel (Author) / Abbas, James (Thesis director) / Crook, Sharon (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The sport of Ultimate, formerly known as Ultimate Frisbee™, spread around the world in the mid-seventies and was considered an alternative sport that embraced a more casual atmosphere than other traditional, competitive sports. Ultimate is now receiving national and international attention as a competitive sport, with broadcasts of games on networks such as ESPN. As it transitions into a mainstream sport while attempting to maintain its alternative roots, it is possible that there are contrasting opinions between those who want to bring it further into the mainstream and those who want to maintain as much as possible of the original, alternative culture. In this work, we surveyed members of the Ultimate community for their perspectives on the unique culture of Ultimate.
Because the Ultimate community considers itself to be progressive, despite its largely Caucasian makeup, one topic of exploration was the political landscape of the Ultimate community. A second unique aspect of ultimate is the system for enforcing rules used by the players on the field, known as the spirit of the game. This system replaces referees and creates an ethical dynamic both during play and within the community that is not found in other sports. The last major topic of study here is the self-perception of the players as athletes. Because Ultimate continues to maintain a reputation as an alternative sport, athletes may perceive themselves differently than in more established sports.
When asked if Ultimate players perceived the Ultimate community as accepting of athletes who are people of color (POC) or members of the lesbian, gay, bisexual, or transgender community (LGBT), the community reported being accepting of all minorities. However, acceptance of POC athletes was rated significantly lower than the acceptance of LGBT athletes. When asked about comradery, the respondents rated comradery higher within the Ultimate community than in other sports. When asked how impartial players were in Ultimate compared to other sports, players with more experience tended to report perceiving themselves as more impartial. All demographics reported being more impartial in Ultimate than in other athletics. When asked about the seriousness of Ultimate, those who had not played another sport considered Ultimate to be more serious than those who had played another sport. In addition, players with more years of Ultimate experience also considered it to be more serious than those with fewer years of experience. Overall, additional studies on Ultimate culture are needed in order to obtain more viewpoints, as there is a lack of research in this field for comparison.
Because the Ultimate community considers itself to be progressive, despite its largely Caucasian makeup, one topic of exploration was the political landscape of the Ultimate community. A second unique aspect of ultimate is the system for enforcing rules used by the players on the field, known as the spirit of the game. This system replaces referees and creates an ethical dynamic both during play and within the community that is not found in other sports. The last major topic of study here is the self-perception of the players as athletes. Because Ultimate continues to maintain a reputation as an alternative sport, athletes may perceive themselves differently than in more established sports.
When asked if Ultimate players perceived the Ultimate community as accepting of athletes who are people of color (POC) or members of the lesbian, gay, bisexual, or transgender community (LGBT), the community reported being accepting of all minorities. However, acceptance of POC athletes was rated significantly lower than the acceptance of LGBT athletes. When asked about comradery, the respondents rated comradery higher within the Ultimate community than in other sports. When asked how impartial players were in Ultimate compared to other sports, players with more experience tended to report perceiving themselves as more impartial. All demographics reported being more impartial in Ultimate than in other athletics. When asked about the seriousness of Ultimate, those who had not played another sport considered Ultimate to be more serious than those who had played another sport. In addition, players with more years of Ultimate experience also considered it to be more serious than those with fewer years of experience. Overall, additional studies on Ultimate culture are needed in order to obtain more viewpoints, as there is a lack of research in this field for comparison.
ContributorsRandall, Sean Edward (Co-author) / Furey, Michael (Co-author) / Mebane, Tyler (Co-author) / Crook, Sharon (Thesis director) / Arrowsmith, Ramon (Committee member) / Simeone, Michael (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Ion channels in the membranes of cells in the body allow for the creation of action potentials from external stimuli, allowing us to sense our surroundings. One particular channel, TRPM8, is a trans-membrane ion channel believed to be the primary cold sensor in humans. Despite this important biological role and intense study of the channel, TRPM8 is not fully understood mechanistically and has not been accurately modeled. Existing models of TRPM8 fail to account for menthol activation of the channel. In this paper we re-implement an established whole cell model for TRPM8 with gating by both voltage and temperature. Using experimental data obtained from the Van Horn lab at Arizona State University, we refined the model to represent more accurately the dynamics of the human TRPM8 channel and incorporate the channel activation through menthol agonist binding. Our new model provides a large improvement over preexisting models, and serves as a basis for future incorporation of other channel activators of TRPM8 and for the modeling of other channels in the TRP family.
ContributorsAckerman, David (Author) / Crook, Sharon (Thesis director) / Van Horn, Wade (Committee member) / School of Earth and Space Exploration (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Epilepsy is a complex neurological disease that affects one in twenty-six people. Despite this prevalence, it is very difficult to diagnose. EpiFinder, Inc. has created an app to better diagnose epilepsy through the use of an epilepsy focused ontology and a heuristic algorithm. Throughout this project, efforts were made to improve the user interface and robustness of the EpiFinder app in order to ease usability and increase diagnostic accuracy. A general workflow of the app was created to aid new users with navigation of the app’s screens. Additionally, numerous diagnostic guidelines provided by the International League Against Epilepsy as well as de-identified case studies were annotated using the Knowtator plug-in in Protégé 3.3.1, where new terms not currently represented in the seizure and epilepsy syndrome ontology (ESSO) were identified for future integration into the ontology. This will help to increase the confidence level of the differential diagnosis reached. A basic evaluation of the user interface was done to provide feedback for the developers for future iterations of the app. Significant efforts were also made for better incorporation of the app into a physician’s typical workflow. For instance, an ontology of a basic review of systems of a medical history was built in Protégé 4.2 for later integration with the ESSO, which will help to increase efficiency and familiarity of the app for physician users. Finally, feedback regarding utility of the app was gathered from an epilepsy support group. These points will be taken into consideration for development of patient-based features in future versions of the EpiFinder app. It is the hope that these various improvements of the app will contribute to a more efficient, more accurate diagnosis of epilepsy patients, resulting in more appropriate treatments and an overall increased quality of life.
ContributorsCsernak, Lidia Maria (Author) / Crook, Sharon (Thesis director) / Greger, Bradley (Committee member) / Yao, Robert (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
There are several challenges to accurately inferring levels of transcription using RNA-sequencing (RNA-seq) data, including detecting and correcting for reference genome mapping bias. One potential confounder of RNA-seq analysis results from the application of a standardized pipeline to samples of different sexes in species with chromosomal sex determination. The homology between the human X and Y chromosomes will routinely cause mismapping to occur, artificially biasing estimates of sex-biased gene transcription. For this reason we tested sex-specific mapping scenarios in humans on RNA-seq samples from the brains of 5 genetic females and 5 genetic males to assess how inferences of differential gene expression patterns change depending on the reference genome. We first applied a mapping protocol where we mapped all individuals to the entire human reference genome (complete), including the X and Y chromosomes, and computed differential expression between the set of genetic male and genetic female samples. We next mapped the genetic female samples (46,XX) to the human reference genome with the Y chromosome removed (Y-excluded) and the genetic male samples (46, XY) to the human reference genome (including the Y chromosome), but with the pseudoautosomal regions of the Y chromosome hard-masked (YPARs-masked) for the two sex-specific mappings. Using the complete and sex-specific mapping protocols, we compared the differential expression measurements of genetic males and genetic females from cuffDiff outputs. The second strategy called 33 additional genes as being differentially expressed between the two sexes when compared to the complete mapping protocol. This research provides a framework for a new standard of reference genome mappings to correct for sex-biased gene expression estimates that can be used in future studies.
ContributorsBrotman, Sarah Marie (Author) / Wilson Sayres, Melissa (Thesis director) / Crook, Sharon (Committee member) / Webster, Timothy (Committee member) / School of Life Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Optogenetics presents the ability to control membrane dynamics through the usage of transfected proteins (opsins) and light stimulation. However, as the field continues to grow, the original biological and stimulation tools used have become dated or limited in their uses. The usage of Organic Light Emitting Diodes (OLEDs) in optical stimulation offers greater resolution, finer control of pixel arrays, and the increased functionality of a flexible display at the cost of lower irradiance power density. This study was done to simulate methods using genetic and optical tools towards decreasing the threshold irradiance needed to initiate an action potential in a ChR2 expressing neuron. Simulations show that pulsatile stimulation can decrease threshold irradiances by increasing the overall duration of stimulus while keeping individual pulse durations below 5 ms. Furthermore, the redistribution of Channelrhodopsin-2 (ChR2) to the apical dendrites and a change in wavelength to 625 nm both result in lower threshold irradiances. However, the model used has many discrepancies and has room for improvement in areas such as the light distribution model and ChR2 dynamics. The simulations run with this model however still present valuable insight and knowledge towards the usage of new stimulation methods and revisions on existing protocols.
ContributorsKyeh, James (Author) / Muthuswamy, Jitendran (Thesis director) / Crook, Sharon (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05