A Computational Framework for Myelin as a Regulator of Temporal Integration, Neuronal Excitability, and Synaptic Plasticity

Abstract

Myelin regulates neural signaling not only by enabling fast conduction but also by dynamically tuning axonal conduction velocity (CV) and thereby shaping spike timing. While activity-dependent myelination is thought to optimize neural communication, how changes in myelin translate into altered single-cell dynamics and plasticity remains unclear. Using a computational modeling approach, we show that disruptions of axonal CV reorganize presynaptic input correlations, leading to systematic changes in postsynaptic excitability, excitation–inhibition balance, and spike-timing-dependent plasticity. By spanning CV regimes associated with healthy myelination, demyelination, and excessive myelination, our simulations illustrate how both deficient and excessive CV could induce maladaptive neuronal dynamics. The incorporation of firing-rate homeostasis into our models further suggests distinct neuronal dynamic consequences for acute versus chronic myelin disruption. Ultimately, these results suggest that axonal CV may serve as a key mechanistic link between myelin plasticity and neural computation, offering a principled framework to interpret the functional consequences of myelin dysregulation in health and disease.