The axon initial segment (AIS) specifies in vertebrate neurons a single domain for the final integration of synaptic input and the initiation of action potentials (APs) ( 1, 2). Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.

In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code.

Dendrite vs axon