Action potential initiation and propagation: Upstream influences on neurotransmission

Axonal action potentials initiate the cycle of synaptic communication that is key to our understanding of nervous system functioning. The field has accumulated vast knowledge of the signature action potential waveform, firing patterns, and underlying channel properties of many cell types, but in most cases this information comes from somatic intracellular/whole-cell recordings, which necessarily measure a mixture of the currents compartmentalized in the soma, dendrites, and axon. Because the axon in many neuron types appears to be the site of lowest threshold for action potential initiation, the channel constellation in the axon is of particular interest. However, the axon is more experimentally inaccessible than the soma or dendrites. Recent studies have developed and applied single-fiber extracellular recording, direct intracellular recording, and optical recording techniques from axons toward understanding the behavior of the axonal action potential. We are starting to understand better how specific channels and other cellular properties shape action potential threshold, waveform, and timing: key elements contributing to downstream transmitter release. From this increased scrutiny emerges a theme of axons with more computational power than in traditional conceptualizations.