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.

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“…Previous modelling showed that these connections contribute to the synchronous recruitment of rhythmic firing in the whole population (Hull et al . ). Using this previous hdIN population model with mutual electrical coupling and excitatory synaptic connections (Fig.…”

“…However, the recruitment of reticulospinal hdINs on one side of the body by hexN excitation might also be influenced by their mutual electrical coupling and excitatory synaptic connections . Previous modelling showed that these connections contribute to the synchronous recruitment of rhythmic firing in the whole population (Hull et al 2015). Using this previous hdIN population model with mutual electrical coupling and excitatory synaptic connections ( Fig.…”

“…E, histogram of all hexN firing times in 30 trials of a single network. F, model of a population of 30 hdINs with electrical coupling and feedback glutamate excitation (Hull et al 2015) excited by hexN spikes at times determined by the hexN recurrent network model. G-I, overlapped voltage records of all 30 hdINs in response to hexN excitation in one trial.…”

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“…Modelling of the hindbrain dIN population has shown that, without electrical coupling, recruitment is gradual and often incomplete, whereas, with electrical coupling, recruitment follows a step function: where dINs are recruited all‐or‐none (Hull et al . ). This is exactly what is needed for a tadpole to decide to swim.…”

“…Modelling of the dIN population response to sensory input has shown that electrical coupling between dINs is critical to this all‐or‐none pattern of recruitment when swimming starts (Hull et al . ). Our work has defined how stimulation of trigeminal head‐skin afferents can activate a trigeminal nucleus and the reticulospinal dINs to initiate swimming on the stimulated side of the body.…”