Differences in action potential propagation speed and axon initial segment plasticity between neurons from Sprague-Dawley rats and C57BL/6 mice

Action potentials (APs) in neurons are generated at the axon initial segment (AIS). AP dynamics, including initiation and propagation, are intimately associated with neuronal excitability and neurotransmitter release kinetics. Most learning and memory studies at the single-neuron level have relied on the use of animal models, most notably rodents. Here, we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley (SD) rats and C57BL/6 (C57) mice with genetically encoded voltage indicator (GEVI)-based voltage imaging. Our data showed that APs traveled bidirectionally in neurons from both species; forward-propagating APs (fpAPs) had a different speed than backpropagating APs (bpAPs). Additionally, we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites. Compared with rat neurons, mouse neurons exhibited higher bpAP speed and lower fpAP speed, more distally located ankyrin G (AnkG) in AISs, and longer Nav1.2 lengths in AISs. Moreover, during AIS plasticity, AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons; in mouse neurons, however, they showed a longer AnkG-labeled length and more distal Nav1.2 location. Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds, different AnkG and Nav1.2 patterns in the AIS, and different AIS plasticity properties, indicating that comparisons between these species must be carefully considered.