Matching Items (9)

158884-Thumbnail Image.png

Understanding Cortical Neuron Dynamics through Simulation-Based Applications of Machine Learning

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

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.

Contributors

Agent

Created

Date Created
  • 2020

152362-Thumbnail Image.png

Time-dependent models of signal transduction networks

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

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.

Contributors

Agent

Created

Date Created
  • 2013

152845-Thumbnail Image.png

Stoichiometric producer-grazer models, incorporating the effects of excess food-nutrient content on grazer dynamics

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

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.

Contributors

Agent

Created

Date Created
  • 2014

158296-Thumbnail Image.png

Thermal Drainage Flow of a Viscous Gas From a Semi-Sealed Narrow Channel

Description

Drainage flow of a viscous compressible gas from a semi-sealed narrow conduit is a pore-scale model for studying the fundamental flow physics of fluid recovery from a porous reservoir without

Drainage flow of a viscous compressible gas from a semi-sealed narrow conduit is a pore-scale model for studying the fundamental flow physics of fluid recovery from a porous reservoir without using fluid injection. Thermal effect has been routinely neglected for these flows in the traditional petroleum engineering literature. Since the motion is entirely driven by volumetric expansion, temperature change always accompanies the density change. This thesis examines such thermal effects on the drainage flow.

Thermal drainage flow is first studied by simultaneously solving the linearized continuity, momentum and energy equations for adiabatic walls. It is shown that even in the absence of an imposed temperature drop, gas expansion induces a transient temperature decrease inside the channel, which slows down the drainage process compared to the isothermal model and Lighthill’s model. For a given density drop, gas drains out faster as the initial-to-final temperature ratio increases; and the transient density can undershoot the final equilibrium value. A parametric study is then carried out to explore the influence of various thermal boundary conditions on drainage flow. It is found that as the wall transitions from adiabatic to isothermal condition, the excess density changes from a plane wave solution to a non-plane wave solution and the drainage rate increases. It is shown that when the exit is also cooled and the wall is non-adiabatic, the total recovered fluid mass exceeds the amount based on the isothermal theory which is determined by the initial and final density difference alone. Finally, a full numerical simulation is conducted to mimic the channel-reservoir system using the finite volume method. The Ghost-Cell Navier-Stokes Characteristic Boundary Condition technique is applied at the far end of the truncated reservoir, which is an open boundary. The results confirm the conclusions of the linear theory.

Contributors

Agent

Created

Date Created
  • 2020

153017-Thumbnail Image.png

Analysis of signal propagation and excitability in computational models of an identified Drosophila motoneuron

Description

Cell morphology and the distribution of voltage gated ion channels play a major role in determining a neuron's firing behavior, resulting in the specific processing of spatiotemporal synaptic input patterns.

Cell morphology and the distribution of voltage gated ion channels play a major role in determining a neuron's firing behavior, resulting in the specific processing of spatiotemporal synaptic input patterns. Although many studies have provided insight into the computational properties arising from neuronal structure as well as from channel kinetics, no comprehensive theory exists which explains how the interaction of these features shapes neuronal excitability. In this study computational models based on the identified Drosophila motoneuron (MN) 5 are developed to investigate the role of voltage gated ion channels, the impact of their densities and the effects of structural features.

First, a spatially collapsed model is used to develop voltage gated ion channels to study the excitability of the model neuron. Changing the channel densities reproduces different in situ observed firing patterns and induces a switch from resonator to integrator properties. Second, morphologically realistic multicompartment models are studied to investigate the passive properties of MN5. The passive electrical parameters fall in a range that is commonly observed in neurons, MN5 is spatially not compact, but for the single subtrees synaptic efficacy is location independent. Further, different subtrees are electrically independent from each other. Third, a continuum approach is used to formulate a new cable theoretic model to study the output in a dendritic cable with many subtrees, both analytically and computationally. The model is validated, by comparing it to a corresponding model with discrete branches. Further, the approach is demonstrated using MN5 and used to investigate spatially distributions of voltage gated ion channels.

Contributors

Agent

Created

Date Created
  • 2014

151575-Thumbnail Image.png

Drift-diffusion simulation of the ephaptic effect in the triad synapse of the retina

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

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.

Contributors

Agent

Created

Date Created
  • 2013

156933-Thumbnail Image.png

A rabies model with distributed latent period and territorial and diffusing rabid foxes

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

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.

Contributors

Agent

Created

Date Created
  • 2018

151528-Thumbnail Image.png

Microchannel flow boiling enhancement via cross-sectional expansion

Description

The heat transfer enhancements available from expanding the cross-section of a boiling microchannel are explored analytically and experimentally. Evaluation of the literature on critical heat flux in flow boiling and

The heat transfer enhancements available from expanding the cross-section of a boiling microchannel are explored analytically and experimentally. Evaluation of the literature on critical heat flux in flow boiling and associated pressure drop behavior is presented with predictive critical heat flux (CHF) and pressure drop correlations. An optimum channel configuration allowing maximum CHF while reducing pressure drop is sought. A perturbation of the channel diameter is employed to examine CHF and pressure drop relationships from the literature with the aim of identifying those adequately general and suitable for use in a scenario with an expanding channel. Several CHF criteria are identified which predict an optimizable channel expansion, though many do not. Pressure drop relationships admit improvement with expansion, and no optimum presents itself. The relevant physical phenomena surrounding flow boiling pressure drop are considered, and a balance of dimensionless numbers is presented that may be of qualitative use. The design, fabrication, inspection, and experimental evaluation of four copper microchannel arrays of different channel expansion rates with R-134a refrigerant is presented. Optimum rates of expansion which maximize the critical heat flux are considered at multiple flow rates, and experimental results are presented demonstrating optima. The effect of expansion on the boiling number is considered, and experiments demonstrate that expansion produces a notable increase in the boiling number in the region explored, though no optima are observed. Significant decrease in the pressure drop across the evaporator is observed with the expanding channels, and no optima appear. Discussion of the significance of this finding is presented, along with possible avenues for future work.

Contributors

Agent

Created

Date Created
  • 2013

152014-Thumbnail Image.png

A neuronal network model of Drosophila antennal lobe

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

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.

Contributors

Agent

Created

Date Created
  • 2013