Computational Model of Parkinson's Disease Pathology in Olfactory Bulb Predicts Localization of Neural Activity and Disruption to Oscillatory Behavior

Abstract

Calcium ions are key signaling molecules in dendritic spines, the small neurotransmitter-receiving protrusions along dendrites. Their dynamics have been shown to regulate many downstream phenomena including synaptic plasticity and learning. Previously we and others have shown that the subcellular morphology of spines can affect signaling dynamics of Ca 2þ and cAMP. In this work we construct a reaction-diffusion Partial Differential Equation (PDE) model of the dynamics of calcium in response to varied electrical stimuli. On realistic mesh geometries of dendritic spines generated from 3D electron micrographs via our open-source workflow including softwares IMOD, GAMer 2, and Blender, the PDEs are solved using FEniCS, an open-source finite element solver. The resulting simulations across many dendritic spines are analyzed for correlations between calcium signals and spine geometries. We posit that these robust ultrastructure-signaling relationships represent possible mechanisms of how dendritic spines can learn and process information.