Single-axon action potentials in the rat hippocampal cortex

Whether all action potentials propagate faithfully throughout axon arbors in the mammalian CNS has long been debated, and remains an important issue because many synapses occur far from the soma along extremely thin, unmyelinated, varicosity-laden branches of axon arbors. We detected unitary action potentials along individual axon branches of adult hippocampal CA3 pyramidal cells using extracellular electrodes, and analysed their conduction across long distances (mean, 2.1 mm) at 22 and 37°C. Axons nearly always transmitted low-frequency impulses. At higher frequencies, most axons also transmitted impulses with striking fidelity. However, at paired-pulse frequencies in the hundreds of kilohertz range, axons exhibited variability: refractory periods ranged from 2.5 to 10 ms at 37°C and from 5 to 40 ms at 22°C. Although the basis for the refractory period variability could not be determined, these limits overlap with CA3 spike frequencies observed in vivo, raising the possibility that some axonal branches act as filters for the higher-order spikes in bursts, in contrast to the observed first-spike reliability. These results extend the observations of propagation reliability to a much longer distance and higher frequency domain than previously reported, and suggest a high safety factor for action potential propagation along thin, varicose axons.