Dynamics of Excitability in Axonal Trees
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We report that axons of cortical neurons, structurally intricate excitable media, maintain somatic spike timing with high fidelity during spontaneous network activity, even at short (2–3 msec) inter-spike intervals. However, long series of external stimulation at physiological frequencies expose a vulnerability that varies depending on distance and branching. At 10 Hz, propagation delays increase within seconds, and failures accumulate over time, particularly in distal axonal branches. These effects are negligible at frequencies of 1–4 Hz. We attribute this phenomenon to the gradual and cumulative inactivation of sodium channels at vulnerable sites. Simulations incorporating this mechanism replicate the observed dynamics. Our findings underscore a limit on axonal reliability. To the extent that a sustained (seconds) drive at ca. 10 Hz or higher is physiologically feasible, axons should be regarded as active, heterogeneous structures with context-sensitive excitability.
Significance Statement
Axons are considered reliable carriers of action potentials from the neuron cell body to respective targets. We show that this reliability holds during spontaneous activity, even at short intervals between spikes. However, sustained stimulation at physiological frequencies (1–10 Hz) compromises reliability. At 10 Hz, some action potentials are delayed or fail outright, with effects more prominent in distant axon branches and higher branch ranks. Simulations of axonal propagation convolved with slow inactivation replicate these phenomena. Our findings suggest that axons are altogether reliable, and, to the extent that sustained drive at ≳10 Hz over seconds or beyond is physiologically relevant to cortical networks in vivo , axons should be regarded for such regimes as dynamic structures with activity history-dependent excitability.
