Dynamics of excitability in axonal trees

We report that axons of cortical neurons, structurally intricate excitable media, maintain remarkably high fidelity in transmitting somatic spike timing, even during complex spontaneous network activity that includes extremely short (2–3 ms) interspike intervals. This robustness underscores their function as reliable conducting devices under physiological conditions. It is nevertheless well established that under artificially imposed, high-rate pulsing stimuli, axonal conduction can fail, with vulnerability depending on distance and branching. In line with this, we demonstrate that conduction failures can also occur at frequencies as low as 10 Hz, provided that stimulation is sustained for several seconds. Under these conditions, propagation delays increase and failures accumulate, particularly in distal branches, whereas effects are negligible at 1–4 Hz. Simulations incorporating cumulative sodium channel inactivation at vulnerable sites reproduce these dynamics. Our findings refine the view of axons as active, heterogeneous structures: they are exceptionally reliable across most physiological regimes, yet exhibit limits under prolonged or extreme stimulation, a regime that is critical for understanding axonal excitability, especially during sustained drive or in pathological conditions.