Electro-diffusive modeling and the role of spine geometry on action potential propagation in neurons

TL;DR

This paper develops a high-fidelity electro-diffusive model using Poisson-Nernst-Planck theory to simulate action potential propagation in neurons, emphasizing the impact of dendritic spine geometry and ion channel distribution.

Contribution

It introduces a comprehensive numerical model integrating dendritic spines, soma, and axon regions to study neuronal electrical signaling with detailed geometry considerations.

Findings

Spine neck length and radius significantly influence action potential initiation.

Ion channel density at the axon hillock affects propagation dynamics.

The model accurately simulates forward and back propagation of action potentials.

Abstract

Electrical signaling in the brain plays a vital role to our existence but at the same time, the fundamental mechanism of this propagation is undeciphered. Notable advancements have been made in the numerical modeling supplementing the related experimental findings. Cable theory based models provided a significant breakthrough in understanding the mechanism of electrical propagation in the neuronal axons. Cable theory, however, fails for thin geometries such as a spine or a dendrite of a neuron, amongst its other limitations. Recently, the spatiotemporal propagation has been precisely modeled using the Poisson-Nernst-Planck (PNP) electro-diffusive theory in the neuronal axons as well as the dendritic spines respectively. Patch clamp and voltage imaging experiments have extensively aided the study of action potential propagation exclusively for the neuronal axons but not the dendritic spines because of the challenges linked with their thin geometry. Assisted by the super-resolution microscopes and the voltage dyeing experiments, it has become possible to precisely measure the voltage in the dendritic spines. This has facilitated the requirement of a high fidelity numerical frame that is capable of acting as a digital twin. Here, using the PNP theory, we integrate the dendritic spine, soma and the axon region to numerically model the propagation of excitatory synaptic potential in a complete neuronal geometry with the synaptic input at the spines, potential initiating at the axon hillock and propagating through the neuronal axon. The model outputs the forward propagation of the action potential along the neuronal axons as well as the back propagation into the spines. We point out the significance of the intricate geometry of the dendritic spines, namely the spine neck length and radius, and the ion channel density in the axon hillock to the action potential initiation and propagation.