Modeling action potential generation during single and dual electrode stimulation of CA3 axons in hippocampal slice

Despite widespread use of electrical stimulation of hippocampal brain slices, the precise sites of action potential initiation and propagation are unknown. To better understand these sites, we modeled axon recruitment by coupling stimulation-induced electric potential fields to biophysical models of CA3 axon arbors in mouse hippocampal brain slices. Geometrically realistic CA3 axon arbors were generated from prior anatomic observations. For single electrode stimulation, 95% of initiation sites were no further than 135 μm away and propagation sites were no further than 875 μm. Using dual electrode stimulation, additional axon arbor pieces were recruited, an effect that increased with distance between stimulating electrodes.