Axons compensate for biophysical constraints of variable size to uniformize their action potentials.

Active conductances tune the kinetics of axonal action potentials (APs) to support specialized functions of neuron types. However, the temporal characteristics of voltage signals strongly depend on the size of neuronal structures, as capacitive and resistive effects slow down voltage discharges in the membranes of small elements. Axonal action potentials are particularly sensitive to these inherent biophysical effects because of the large diameter variabilities within individual axons, potentially implying bouton size-dependent synaptic effects. However, using direct patch-clamp recordings and voltage imaging in small hippocampal axons in acute slices from rat brains, we demonstrate that AP shapes remain uniform within the same axons, even across an order of magnitude difference in caliber. Our results show that smaller axonal structures have more Kv1 potassium channels that locally re-accelerate AP repolarization and contribute to size-independent APs, while they do not preclude the plasticity of AP shapes. Thus, size-independent axonal APs ensure consistent digital signals for each synapse within axons of same types.