Excitability Tuning of Axons by Afterdepolarization

The axon provides a sole output of the neuron which propagates action potentials reliably to the axon terminal and transmits neuronal information to the postsynaptic neuron across the synapse. A classical view of neuronal signaling is based on these two processes, namely binary (all or none) signaling along the axon and graded (tunable) signaling at the synapse. Recent studies, however, have revealed that the excitability of the axon is subject to dynamic tuning for a short period after axonal action potentials. This was first described as post-spike hyperexcitability, as measured by the changes in stimulus threshold for a short period after an action potential. Later on, direct recordings from central nervous system (CNS) axons or axon terminals using subcellular patch-clamp recording showed that axonal spikes are often followed by afterdepolarization (ADP) lasting for several tens of milliseconds and has been suggested to mediate post-spike hyperexcitability. In this review article, I focused on the mechanisms as well as the functional significance of ADP in fine-scale modulation of axonal spike signaling in the CNS, with special reference to hippocampal mossy fibers, one of the best-studied CNS axons. As a common basic mechanism underlying axonal ADP, passive propagation by the capacitive discharge of the axonal membrane as well as voltage-dependent K⁺ conductance underlies the generation of ADP. Small but prolonged axonal ADP lasting for several tens of milliseconds may influence the subsequent action potential and transmitter release from the axon terminals. Both duration and amplitude of axonal spike are subject to such modulation by preceding action potential-ADP sequence, deviating from the conventional assumption of digital nature of axonal spike signaling. Impact on the transmitter release is also discussed in the context of axonal spike plasticity. Axonal spike is subject to dynamic control on a fine-scale and thereby contributes to the short-term plasticity at the synapse.