arXiv subjects

Michael A. Henson

Publications and source records attributed to Michael A. Henson.

2 recordsLinked to original sources

arXiv2022

Limits of Entrainment of Circadian Neuronal Networks

Circadian rhythmicity lies at the center of various important physiological and behavioral processes in mammals, such as sleep, metabolism, homeostasis, mood changes and more. It has been shown that this rhythm arises from self-sustained biomolecular oscillations of a neuronal network located in the Suprachiasmatic Nucleus (SCN). Under normal circumstances, this network remains synchronized to the day-night cycle due to signaling from the retina. Misalignment of these neuronal oscillations with the external light signal can disrupt numerous physiological functions and take a long-lasting toll on health and well-being. In this work, we study a modern computational neuroscience model to determine the limits of circadian synchronization to external light signals of different frequency and duty cycle. We employ a matrix-free approach to locate periodic steady states of the high-dimensional model for various driving conditions. Our algorithmic pipeline enables numerical continuation and construction of bifurcation diagrams w.r.t. forcing parameters. We computationally explore the effect of heterogeneity in the circadian neuronal network, as well as the effect of corrective therapeutic interventions, such as that of the drug molecule Longdaysin. Lastly, we employ unsupervised learning to construct a data-driven embedding space for representing neuronal heterogeneity.

q-bio.NC↗

arXiv2006

Heterogeneous Cell Population Dynamics: Equation-Free Uncertainty Quantification Computations

We propose a computational approach to modeling the collective dynamics of populations of coupled heterogeneous biological oscillators. In contrast to Monte Carlo simulation, this approach utilizes generalized Polynomial Chaos (gPC) to represent random properties of the population, thus reducing the dynamics of ensembles of oscillators to dynamics of their (typically significantly fewer) representative gPC coefficients. Equation-Free (EF) methods are employed to efficiently evolve these gPC coefficients in time and compute their coarse-grained stationary state and/or limit cycle solutions, circumventing the derivation of explicit, closed-form evolution equations. Ensemble realizations of the oscillators and their statistics can be readily reconstructed from these gPC coefficients. We apply this methodology to the synchronization of yeast glycolytic oscillators coupled by the membrane exchange of an intracellular metabolite. The heterogeneity consists of a single random parameter, which accounts for glucose influx into a cell, with a Gaussian distribution over the population. Coarse projective integration is used to accelerate the evolution of the population statistics in time. Coarse fixed-point algorithms in conjunction with a Poincaré return map are used to compute oscillatory solutions for the cell population and to quantify their stability.

q-bio.QM↗