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.

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.

The theme for this work is the development of fast numerical algorithms for sparse optimization as well as their applications in medical imaging and source localization using sensor array processing. Due to the recently proposed theory of Compressive Sensing (CS), the $\ell_1$ minimization problem attracts more attention for its ability to exploit sparsity. Traditional interior point methods encounter difficulties in computation for solving the CS applications. In the first part of this work, a fast algorithm based on the augmented Lagrangian method for solving the large-scale TV-$\ell_1$ regularized inverse problem is proposed. Specifically, by taking advantage of the separable structure, the original problem can be approximated via the sum of a series of simple functions with closed form solutions. A preconditioner for solving the block Toeplitz with Toeplitz block (BTTB) linear system is proposed to accelerate the computation. An in-depth discussion on the rate of convergence and the optimal parameter selection criteria is given. Numerical experiments are used to test the performance and the robustness of the proposed algorithm to a wide range of parameter values. Applications of the algorithm in magnetic resonance (MR) imaging and a comparison with other existing methods are included. The second part of this work is the application of the TV-$\ell_1$ model in source localization using sensor arrays. The array output is reformulated into a sparse waveform via an over-complete basis and study the $\ell_p$-norm properties in detecting the sparsity. An algorithm is proposed for minimizing a non-convex problem. According to the results of numerical experiments, the proposed algorithm with the aid of the $\ell_p$-norm can resolve closely distributed sources with higher accuracy than other existing methods.