The pattern of ion channels in the axon initial segment affects feedback sent to dendrites.

What is it about?

Neurons use sodium ion currents, controlled by a neuron’s voltage, to trigger signals called action potentials (APs). These APs typically result from synaptic input from other neurons onto the dendrites and soma. An AP is generated at the axon initial segment (AIS) just beyond the soma. From there, it travels down the axon to other cells, but can also propagate “backwards” into the soma and dendrites. This “backpropagation” allows the neuron to compare the timing of outgoing and incoming signals at synapses where input was received, a feedback process that modifies its connections to other neurons (spike-timing-dependent synaptic plasticity) which is a mechanism for learning. It is puzzling that in many neurons, sodium ion channels come in two types: high-voltage threshold channels clustered near the soma where the AIS begins, and low-voltage ones further away towards the axon. This separation changes in the early development of the animal, which raises the question of its role in backpropagation. We constructed detailed mathematical models to explore how separation affects backpropagation. Separation either impedes or enhances backpropagation, depending on whether the AP results from input to the soma or dendrites or, less typically, input received in the axon. This is explained by the different effects the separation has on two key kinetic processes that govern sodium currents.

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Photo by Robina Weermeijer on Unsplash

Photo by Robina Weermeijer on Unsplash

Why is it important?

Recently observed developmental changes to the spatial separation and relative proportions of two key sodium channel subtypes in the AIS differentially impact activation and availability. Our simulations predict that the effects on backpropagation, and potentially learning via its putative role in synaptic plasticity (e.g. through spike-timing-dependent plasticity), are opposite for somatodendritic versus axonal stimulation, which should inform hypotheses about the impact of the developmentally regulated subcellular localization of these ion channels.