Ephaptic coupling distance between myelinated axons is not static but a dynamic function of neural code and axonal plasticity

In this paper, using resistor-capacitor modelling, for the first time we established a generalised theoretical framework to quantitatively characterise the governing parameters for inducing Action Potential (AP) from one myelinated axon to another via Ephaptic Coupling (EC) phenomenon. Analyses of the model showed that the EC distance is a dynamic function of (1) the instantaneous frequency of the AP train, which in essence represents a neural code, in the driving fibre, (2) the (mis)alignment of the Nodes of Ranvier (NR) between the driving and the driven fibre, and 3) the radii of the driving and the driven NR. The last two factors are intrinsically related to axonal plasticity that takes effect at a longer timescale compared to the first factor. We also showed that a driving NR can induce AP to a maximum of 6 NRs in a homogeneous nerve bundle while in a heterogeneous nerve bundle AP could be induced by one NR to another if the radius of the driven NR is less than 6-times the radius of the driving NR. The set of rules developed in this work gives an objective guideline for (1) understanding how a neural code transmitted by a neural population to another could get modified during its propagation via a nerve bundle connecting them such as, the White Matter Tracts and Spinal Nerves, and 2) selecting appropriate stimulation parameters to dynamically modify neural codes in a nerve bundle for treating various nerve disorders.