Axons in the cerebral cortex receive synaptic input at the axon initial segment almost
exclusively from gamma-aminobutyric acid-releasing (GABAergic) axo-axonic cells (AACs).
The axon has the lowest threshold for action potential generation in neurons; thus,
AACs are considered to be strategically placed inhibitory neurons controlling neuronal
output. However, we found that AACs can depolarize pyramidal cells and can initiate
stereotyped series of synaptic events in rat and human cortical networks because of
a depolarized reversal potential for axonal relative to perisomatic GABAergic inputs.
Excitation and signal propagation initiated by AACs is supported by the absence of
the potassium chloride cotransporter 2 in the axon.
