Spike transmission failures in axons from cortical neurons in vivo

The propagation of action potentials along axons is traditionally considered reliable due to the high safety factor for axonal spike transmission. However, numerical simulations suggest that high-frequency spikes could fail to invade distal axonal branches. To explore this experimentally <i>in vivo</i>, we used an axonal-targeted calcium indicator to image action potentials at axonal terminal branches in the superficial layers of mouse somatosensory cortical neurons. We activated axons with an extracellular electrode, varying stimulation frequencies, and analyzed the images to computationally extract axonal morphologies and associated calcium responses. We found that axonal boutons have higher calcium accumulations than their axonal shafts, as was reported <i>in vitro</i>. However, contrary to previous <i>in vitro</i> results, our data reveal spike failures at high spike frequencies in a significant subset of branches as a function of branching geometry. These findings suggest that axonal morphologies could contribute to signal processing in the cortex.