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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
In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback. This feedback has a number of important physiological consequences. One is called background-induced flicker enhancement (BIFE) in which the onset of dim background enhances

In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback. This feedback has a number of important physiological consequences. One is called background-induced flicker enhancement (BIFE) in which the onset of dim background enhances the center flicker response of horizontal cells. The underlying mechanism for the feedback is still unclear but competing hypotheses have been proposed. One is the GABA hypothesis, which states that the feedback is mediated by gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter released from horizontal cells. Another is the ephaptic hypothesis, which contends that the feedback is non-GABAergic and is achieved through the modulation of electrical potential in the intersynaptic cleft between cones and horizontal cells. In this study, a continuum spine model of the cone-horizontal cell synaptic circuitry is formulated. This model, a partial differential equation system, incorporates both the GABA and ephaptic feedback mechanisms. Simulation results, in comparison with experiments, indicate that the ephaptic mechanism is necessary in order for the model to capture the major spatial and temporal dynamics of the BIFE effect. In addition, simulations indicate that the GABA mechanism may play some minor modulation role.
ContributorsChang, Shaojie (Author) / Baer, Steven M. (Thesis advisor) / Gardner, Carl L (Thesis advisor) / Crook, Sharon M (Committee member) / Kuang, Yang (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Factory production is stochastic in nature with time varying input and output processes that are non-stationary stochastic processes. Hence, the principle quantities of interest are random variables. Typical modeling of such behavior involves numerical simulation and statistical analysis. A deterministic closure model leading to a second

Factory production is stochastic in nature with time varying input and output processes that are non-stationary stochastic processes. Hence, the principle quantities of interest are random variables. Typical modeling of such behavior involves numerical simulation and statistical analysis. A deterministic closure model leading to a second order model for the product density and product speed has previously been proposed. The resulting partial differential equations (PDE) are compared to discrete event simulations (DES) that simulate factory production as a time dependent M/M/1 queuing system. Three fundamental scenarios for the time dependent influx are studied: An instant step up/down of the mean arrival rate; an exponential step up/down of the mean arrival rate; and periodic variation of the mean arrival rate. It is shown that the second order model, in general, yields significant improvement over current first order models. Specifically, the agreement between the DES and the PDE for the step up and for periodic forcing that is not too rapid is very good. Adding diffusion to the PDE further improves the agreement. The analysis also points to fundamental open issues regarding the deterministic modeling of low signal-to-noise ratio for some stochastic processes and the possibility of resonance in deterministic models that is not present in the original stochastic process.
ContributorsWienke, Matthew (Author) / Armbruster, Dieter (Thesis advisor) / Jones, Donald (Committee member) / Platte, Rodrigo (Committee member) / Gardner, Carl (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2015