Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability

Grubb, MS. Burrone, J. (2010) Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature 465: 1070-1074.

Labelling for AIS scaffolding protein ankyrin G shows that the AIS will shift distally when the neuron is over-excited. When excitation is removed AIS will shift back towards the soma.

Movement is governed by Calcium channels and is not influenced by spiking. T- and/or L- type VGCCs. Burst activation of neurons is necessary to get AIS to move as sparse activation does not have much of an effect. This is probably due to different peak-levels of calcium entry.

Patch-clamp shows that distal AIS reduces excitability. Change in threshold of 100 pA. (change in Rm accounts for only 43 pA of 100 pA). Distal AIS lowers spike rate, but large current inputs can overcome deecrease and catch up to proximal AIS.

In supplemental they conclude that this process is a shift in the input-output function of the neuron, as opposed to gain or scaling. In my model, decreasing gc by moving the AIS away would result in a scaling. The fact that more current allows it to catch-up is result of spiking reaching saturation.