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152014-Thumbnail Image.png
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

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
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Description
There has been important progress in understanding ecological dynamics through the development of the theory of ecological stoichiometry. This fast growing theory provides new constraints and mechanisms that can be formulated into mathematical models. Stoichiometric models incorporate the effects of both food quantity and food quality into a single framework

There has been important progress in understanding ecological dynamics through the development of the theory of ecological stoichiometry. This fast growing theory provides new constraints and mechanisms that can be formulated into mathematical models. Stoichiometric models incorporate the effects of both food quantity and food quality into a single framework that produce rich dynamics. While the effects of nutrient deficiency on consumer growth are well understood, recent discoveries in ecological stoichiometry suggest that consumer dynamics are not only affected by insufficient food nutrient content (low phosphorus (P): carbon (C) ratio) but also by excess food nutrient content (high P:C). This phenomenon, known as the stoichiometric knife edge, in which animal growth is reduced not only by food with low P content but also by food with high P content, needs to be incorporated into mathematical models. Here we present Lotka-Volterra type models to investigate the growth response of Daphnia to algae of varying P:C ratios. Using a nonsmooth system of two ordinary differential equations (ODEs), we formulate the first model to incorporate the phenomenon of the stoichiometric knife edge. We then extend this stoichiometric model by mechanistically deriving and tracking free P in the environment. This resulting full knife edge model is a nonsmooth system of three ODEs. Bifurcation analysis and numerical simulations of the full model, that explicitly tracks phosphorus, leads to quantitatively different predictions than previous models that neglect to track free nutrients. The full model shows that the grazer population is sensitive to excess nutrient concentrations as a dynamical free nutrient pool induces extreme grazer population density changes. These modeling efforts provide insight on the effects of excess nutrient content on grazer dynamics and deepen our understanding of the effects of stoichiometry on the mechanisms governing population dynamics and the interactions between trophic levels.
ContributorsPeace, Angela (Author) / Kuang, Yang (Thesis advisor) / Elser, James J (Committee member) / Baer, Steven (Committee member) / Tang, Wenbo (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Modern measurement schemes for linear dynamical systems are typically designed so that different sensors can be scheduled to be used at each time step. To determine which sensors to use, various metrics have been suggested. One possible such metric is the observability of the system. Observability is a binary condition

Modern measurement schemes for linear dynamical systems are typically designed so that different sensors can be scheduled to be used at each time step. To determine which sensors to use, various metrics have been suggested. One possible such metric is the observability of the system. Observability is a binary condition determining whether a finite number of measurements suffice to recover the initial state. However to employ observability for sensor scheduling, the binary definition needs to be expanded so that one can measure how observable a system is with a particular measurement scheme, i.e. one needs a metric of observability. Most methods utilizing an observability metric are about sensor selection and not for sensor scheduling. In this dissertation we present a new approach to utilize the observability for sensor scheduling by employing the condition number of the observability matrix as the metric and using column subset selection to create an algorithm to choose which sensors to use at each time step. To this end we use a rank revealing QR factorization algorithm to select sensors. Several numerical experiments are used to demonstrate the performance of the proposed scheme.
ContributorsIlkturk, Utku (Author) / Gelb, Anne (Thesis advisor) / Platte, Rodrigo (Thesis advisor) / Cochran, Douglas (Committee member) / Renaut, Rosemary (Committee member) / Armbruster, Dieter (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Rabies is an infectious viral disease. It is usually fatal if a victim reaches the rabid stage, which starts after the appearance of disease symptoms. The disease virus attacks the central nervous system, and then it migrates from peripheral nerves to the spinal cord and brain. At the time when

Rabies is an infectious viral disease. It is usually fatal if a victim reaches the rabid stage, which starts after the appearance of disease symptoms. The disease virus attacks the central nervous system, and then it migrates from peripheral nerves to the spinal cord and brain. At the time when the rabies virus reaches the brain, the incubation period is over and the symptoms of clinical disease appear on the victim. From the brain, the virus travels via nerves to the salivary glands and saliva.

A mathematical model is developed for the spread of rabies in a spatially distributed fox population to model the spread of the rabies epizootic through middle Europe that occurred in the second half of the 20th century. The model considers both territorial and wandering rabid foxes and includes a latent period for the infection. Since the model assumes these two kinds of rabid foxes, it is a system of both partial differential and integral equations (with integration

over space and, occasionally, also over time). To study the spreading speeds of the rabies epidemic, the model is reduced to a scalar Volterra-Hammerstein integral equation, and space-time Laplace transform of the integral equation is used to derive implicit formulas for the spreading speed. The spreading speeds are discussed and implicit formulas are given for latent periods of fixed length, exponentially distributed length, Gamma distributed length, and log-normally distributed length. A number of analytic and numerical results are shown pertaining to the spreading speeds.

Further, a numerical algorithm is described for the simulation

of the spread of rabies in a spatially distributed fox population on a bounded domain with Dirichlet boundary conditions. I propose the following methods for the numerical approximation of solutions. The partial differential and integral equations are discretized in the space variable by central differences of second order and by

the composite trapezoidal rule. Next, the ordinary or delay differential equations that are obtained this way are discretized in time by explicit

continuous Runge-Kutta methods of fourth order for ordinary and delay differential systems. My particular interest

is in how the partition of rabid foxes into

territorial and diffusing rabid foxes influences

the spreading speed, a question that can be answered by purely analytic means only for small basic reproduction numbers. I will restrict the numerical analysis

to latent periods of fixed length and to exponentially

distributed latent periods.

The results of the numerical calculations

are compared for latent periods

of fixed and exponentially distributed length

and for various proportions of territorial

and wandering rabid foxes.

The speeds of spread observed in the

simulations are compared

to spreading speeds obtained by numerically solving the analytic formulas

and to observed speeds of epizootic frontlines

in the European rabies outbreak 1940 to 1980.
ContributorsAlanazi, Khalaf Matar (Author) / Thieme, Horst R. (Thesis advisor) / Jackiewicz, Zdzislaw (Committee member) / Baer, Steven (Committee member) / Gardner, Carl (Committee member) / Kuang, Yang (Committee member) / Smith, Hal (Committee member) / Arizona State University (Publisher)
Created2018
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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

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
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Description
Signaling cascades transduce signals received on the cell membrane to the nucleus. While noise filtering, ultra-sensitive switches, and signal amplification have all been shown to be features of such signaling cascades, it is not understood why cascades typically show three or four layers. Using singular perturbation theory, Michaelis-Menten type equations

Signaling cascades transduce signals received on the cell membrane to the nucleus. While noise filtering, ultra-sensitive switches, and signal amplification have all been shown to be features of such signaling cascades, it is not understood why cascades typically show three or four layers. Using singular perturbation theory, Michaelis-Menten type equations are derived for open enzymatic systems. When these equations are organized into a cascade, it is demonstrated that the output signal as a function of time becomes sigmoidal with the addition of more layers. Furthermore, it is shown that the activation time will speed up to a point, after which more layers become superfluous. It is shown that three layers create a reliable sigmoidal response progress curve from a wide variety of time-dependent signaling inputs arriving at the cell membrane, suggesting that natural selection may have favored signaling cascades as a parsimonious solution to the problem of generating switch-like behavior in a noisy environment.
ContributorsYoung, Jonathan Trinity (Author) / Armbruster, Dieter (Thesis advisor) / Platte, Rodrigo (Committee member) / Nagy, John (Committee member) / Baer, Steven (Committee member) / Taylor, Jesse (Committee member) / Arizona State University (Publisher)
Created2013
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Description
It is increasingly common to see machine learning techniques applied in conjunction with computational modeling for data-driven research in neuroscience. Such applications include using machine learning for model development, particularly for optimization of parameters based on electrophysiological constraints. Alternatively, machine learning can be used to validate and enhance techniques for

It is increasingly common to see machine learning techniques applied in conjunction with computational modeling for data-driven research in neuroscience. Such applications include using machine learning for model development, particularly for optimization of parameters based on electrophysiological constraints. Alternatively, machine learning can be used to validate and enhance techniques for experimental data analysis or to analyze model simulation data in large-scale modeling studies, which is the approach I apply here. I use simulations of biophysically-realistic cortical neuron models to supplement a common feature-based technique for analysis of electrophysiological signals. I leverage these simulated electrophysiological signals to perform feature selection that provides an improved method for neuron-type classification. Additionally, I validate an unsupervised approach that extends this improved feature selection to discover signatures associated with neuron morphologies - performing in vivo histology in effect. The result is a simulation-based discovery of the underlying synaptic conditions responsible for patterns of extracellular signatures that can be applied to understand both simulation and experimental data. I also use unsupervised learning techniques to identify common channel mechanisms underlying electrophysiological behaviors of cortical neuron models. This work relies on an open-source database containing a large number of computational models for cortical neurons. I perform a quantitative data-driven analysis of these previously published ion channel and neuron models that uses information shared across models as opposed to information limited to individual models. The result is simulation-based discovery of model sub-types at two spatial scales which map functional relationships between activation/inactivation properties of channel family model sub-types to electrophysiological properties of cortical neuron model sub-types. Further, the combination of unsupervised learning techniques and parameter visualizations serve to integrate characterizations of model electrophysiological behavior across scales.
ContributorsHaynes, Reuben (Author) / Crook, Sharon M (Thesis advisor) / Gerkin, Richard C (Committee member) / Zhou, Yi (Committee member) / Baer, Steven (Committee member) / Armbruster, Hans D (Committee member) / Arizona State University (Publisher)
Created2020