Ionic mechanisms underlying history-dependence of conduction delay in an unmyelinated axon

Axonal conduction velocity can change substantially during ongoing activity, thus modifying spike interval structures and, potentially, temporal coding. We used a biophysical model to unmask mechanisms underlying the history-dependence of conduction. The model replicates activity in the unmyelinated axon of the crustacean stomatogastric pyloric dilator neuron. At the timescale of a single burst, conduction delay has a non-monotonic relationship with instantaneous frequency, which depends on the gating rates of the fast voltage-gated Na⁺ current. At the slower timescale of minutes, the mean value and variability of conduction delay increase. These effects are because of hyperpolarization of the baseline membrane potential by the Na⁺/K⁺ pump, balanced by an h-current, both of which affect the gating of the Na⁺ current. We explore the mechanisms of history-dependence of conduction delay in axons and develop an empirical equation that accurately predicts this history-dependence, both in the model and in experimental measurements.