Thinking About the Nerve Impulse: The Prospects for the Development of a Comprehensive Account of Nerve Impulse Propagation

Abstract

Currently, a scientific debate is ongoing about modeling nerve impulse propagation. One of the models discussed is the celebrated Hodgkin-Huxley model of the action potential, which is central to the electricity-centered conception of the nerve impulse that dominates contemporary neuroscience. However, this model cannot represent the nerve impulse completely, since it does not take into account non-electrical manifestations of the nerve impulse for which there is ample experimental evidence. As a result, alternative models of nerve impulse propagation have been proposed in contemporary (neuro)scientific literature. One of these models is the Heimburg-Jackson model, according to which the nerve impulse is an electromechanical density pulse in the neural membrane. This model is usually contrasted with the Hodgkin-Huxley model and is supposed to potentially be able to replace the latter. However, instead of contrasting these models of nerve impulse propagation, another approach integrates these models in a general unifying model. This general unifying model, the Engelbrecht model, is developed to unify all relevant manifestations of the nerve impulse and their interaction(s). Here, we want to contribute to the debate about modeling nerve impulse propagation by conceptually analyzing the Engelbrecht model. Combining the results of this conceptual analysis with insights from philosophy of science, we make recommendations for the study of nerve impulse propagation. The first conclusion of this analysis is that attempts to develop models that represent the nerve impulse accurately and completely appear unfeasible. Instead, models are and should be used as tools to study nerve impulse propagation for varying purposes, representing the nerve impulse accurately and completely enough to achieve the specified goals. The second conclusion is that integrating distinct models into a general unifying model that provides a consistent picture of nerve impulse propagation is impossible due to the distinct purposes for which they are developed and the conflicting assumptions these purposes often require. Instead of explaining nerve impulse propagation with a single general unifying model, it appears advisable to explain this complex phenomenon using a ‘mosaic’ framework of models in which each model provides a partial explanation of nerve impulse propagation.

Nodes of Ranvier during development and repair in the CNS

“…Their activity largely contributes to repolarizing the nodal membrane during a spike, and is also important for the stabilization of a negative resting potential and maximum spike amplitude 5,6,68,71 . The activity of K2P channels can be diversely regulated to control cellular excitability, notably by force applied directly through the lipid bilayer 162,163 and could serve a mechano-protective role in node of Ranvier or respond to mechanical component of the action potential 164 . Other K + channels also repolarizes membrane at nodes, such as KCa3.1, a calcium-activated potassium channel, which is a key determinant for generation of fast frequency spikes and safe conduction in Purkinje cell axons 165 .…”

On mechanisms of electromechanophysiological interactions between the components of nerve signals in axons

“…The coupling forces [18] have been proposed to model the interaction between the components of the whole ensemble. The criticism on this model [45] is based on the seeming inconsistency of the coupling of the AP and LW described by indicated models. The main point of the criticism is that in the HH model the capacitance of the neural membrane is taken constant [45].…”

“…The criticism on this model [45] is based on the seeming inconsistency of the coupling of the AP and LW described by indicated models. The main point of the criticism is that in the HH model the capacitance of the neural membrane is taken constant [45]. However, it must be noted that in the coupled model one has used the modelling of an AP only for obtaining a correct (measured by numerous experiments) asymmetric shape of an AP with an overshoot and a corresponding ion current.…”

Explaining trans-phase potential differences with membrane theory, association-induction hypothesis and murburn concept

“…Analysis of the TMP has a long history. The pioneering experiments and modeling in the field were done by Hodgkin and Huxley [10][11][12][13][14][15]. They theorized the dynamic facets of the TMP and laid down the foundations of modern electrophysiology.…”