Modelling the Effects of Electrical Coupling between Unmyelinated Axons of Brainstem Neurons Controlling Rhythmic Activity

Abstract

Gap junctions between fine unmyelinated axons can electrically couple groups of brain neurons to synchronise firing and contribute to rhythmic activity. To explore the distribution and significance of electrical coupling, we modelled a well analysed, small population of brainstem neurons which drive swimming in young frog tadpoles. A passive network of 30 multicompartmental neurons with unmyelinated axons was used to infer that: axon-axon gap junctions close to the soma gave the best match to experimentally measured coupling coefficients; axon diameter had a strong influence on coupling; most neurons were coupled indirectly via the axons of other neurons. When active channels were added, gap junctions could make action potential propagation along the thin axons unreliable. Increased sodium and decreased potassium channel densities in the initial axon segment improved action potential propagation. Modelling suggested that the single spike firing to step current injection observed in whole-cell recordings is not a cellular property but a dynamic consequence of shunting resulting from electrical coupling. Without electrical coupling, firing of the population during depolarising current was unsynchronised; with coupling, the population showed synchronous recruitment and rhythmic firing. When activated instead by increasing levels of modelled sensory pathway input, the population without electrical coupling was recruited incrementally to unpatterned activity. However, when coupled, the population was recruited all-or-none at threshold into a rhythmic swimming pattern: the tadpole “decided” to swim. Modelling emphasises uncertainties about fine unmyelinated axon physiology but, when informed by biological data, makes general predictions about gap junctions: locations close to the soma; relatively small numbers; many indirect connections between neurons; cause of action potential propagation failure in fine axons; misleading alteration of intrinsic firing properties. Modelling also indicates that electrical coupling within a population can synchronize recruitment of neurons and their pacemaker firing during rhythmic activity.

Author Summary

Some groups of nerve cells in the brain are connected to each other electrically where their processes make contact and form specialized “gap” junctions. The simplest function of electrical connections is to make activity propagate faster by avoiding the delays resulting from chemical messengers at synaptic connections. In other cases, especially in higher brain regions where more spread out nerve cells may be connected by their axons, the function of electrical coupling is less clear. To understand this type of electrical connection better we have built computer models of a group of electrically coupled nerve cells in the brain which control swimming in very young frog tadpoles. We show that the coupling can be indirect, via other members of the group, and can profoundly influence the properties of the nerve cells which would be recorded during real experiments. The main role of the coupling is to synchronise the firing of the group so they are all recruited together when the tadpole is stimulated and then fire in a rhythm suitable to drive swimming movements. The results from this simple animal raise issues which will help to understand coupling in more complex brains.