Axon Initial Segment

Abstract

The axon initial segment (AIS) is a specialised region of the axon where the action potential is initiated following integration of excitatory and inhibitory inputs. The AIS contains high density of sodium and potassium channels anchored on scaffold proteins, but it also includes receptors to neurotransmitters and neuromodulators. Besides its role in action potential initiation, the AIS constitutes a diffusion barrier that controls cytoplasmic traffic towards the axon. Activity‐dependent plasticity has been recently shown to affect the length and position of the AIS whereas stimulation of ligand‐gated receptors alters the ion channel content of the AIS. Thus, the AIS represents a critical element in neuronal excitability and its plasticity.

Key Concepts

  • The axon initial segment is the site of action potential initiation.
  • It is enriched with high density of voltage‐gated sodium and potassium channels.
  • Ion channels are anchored at the AIS through scaffold proteins.
  • The AIS constitutes a barrier for molecular and cellular traffic from the soma to the axon and is, therefore, essential to maintain axonal identity.
  • The structure and function of the AIS is subject to activity‐dependent plasticity.

Keywords: action potential; ion channels; neuron; excitability; plasticity

Figure 1. Structure and composition of the AIS. Inputs originated from the dendrites are integrated at the AIS where the AP is triggered. The propagation of the spikes to the presynaptic terminal is made possible by nodes of Ranvier, which composition is similar to AIS. The membrane of AIS is characterised by a high concentration of sodium channels (Nav), 50 times higher than in soma. Other potassium and calcium voltage‐gated ion channels (Kv and Cav) contribute to modulate excitability. These channels are anchored and concentrated through scaffold proteins like AnkyrinG and PSD‐93. AnkyrinG is anchored to the AIS actin microfilaments by βIV‐spectrin. Both actin microfilaments and microtubules have distinctive characteristics at the AIS and its contribution to AIS structure and function is still mostly unknown. All this complex structure is modulated through recently identified kinases (such as CK2 or GSK3) and phosphatases (such as calcineurin).
Figure 2. Function of the AIS. (a) Spike initiation in the AIS. Dual AIS‐soma recording from a pyramidal neuron. Left, recording configuration. Right, action potential measured in the soma is slightly delayed compared to that measured in the AIS. (b) Spike threshold at the AIS and the cell body. Simultaneous recording from L5 pyramidal neuron in the AIS (left) and the soma (right). While the rheobase is lower in the AIS compared to the soma, the voltage threshold is higher. Reproduced with permission from Kole and Stuart . © Springer Nature.
Figure 3. Plasticity of the AIS. (a) Elongation of the AIS. Following activity deprivation, the length of the AIS is increased. Reproduced with permission from Kuba et al. . © Springer Nature. (b) Shift in the AIS position. Following activity enhancement, the AIS position is shifted away from the soma. Reproduced with permission from Grubb and Burrone . © Springer Nature. (c) Change in composition of the AIS. Following stimulation of P2X7 receptor, the density of ankyrin G is reduced. Reproduced with permission from Del Puerto et al. . © Oxford University Press.
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Further Reading

Debanne D, Campanac E, Bialowas A, Carlier E and Alacaraz G (2011) Axon physiology. Physiological Reviews 91: 555–602.

Huang CY and Rasband M (2018) Axon initial segments: structure, function, and disease. Annals of the New York Academy of Sciences 1420: 46–61.

Jamann N, Jordan M and Engelhardt M (2018) Activity‐dependent axonal plasticity in sensory systems. Neuroscience 368: 268–282.

Kole MH and Stuart G (2012) Signal processing in the axon initial segment. Neuron 73: 235–247.

Kuba H (2012) Structural tuning and plasticity of the axon initial segment in auditory neurons. Journal of Physiology 590: 5571–5579.

Leterrier C (2018) The axon initial segment: an updated viewpoint. Journal of Neuroscience 38: 2135–2145.

Rama S, Zbili M and Debanne D (2018) Signal propagation along the axon. Current Opinion in Neurobiology 51: 37–44.

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Debanne, Dominique, and Garrido, Juan José(Dec 2018) Axon Initial Segment. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000004]