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

Zool Res. 2022 Jul 18;43(4):615-633. doi: 10.24272/j.issn.2095-8137.2022.121.

Abstract

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.

动作电位产生于神经元的轴突起始节(Axon initial segment , AIS),动作电位的爆发与传播,与神经元兴奋性以及神经递质释放密切相关。神经元水平的学习和记忆研究依赖于许多动物模型的使用,尤其是啮齿类动物。该文中,我们利用基于遗传编码电压指示器的电压成像技术,研究动作电位在Sprague-Dawley(SD)大鼠和C57BL/6(C57)小鼠海马神经元中的爆发和传播。我们的实验数据显示,在两种物种的神经元中动作电位都是双向传播的,其中,沿轴突向下传播动作电位与向胞体往回传播动作电位的速度不同,且树突起源和胞体起源的AIS上动作电位的传播有其独特的性质。与大鼠相比,小鼠神经元表现出较高的回传动作电位速度和较低的下传动作电位速度,锚蛋白G (AnkG)在小鼠神经元的AIS上偏向于远端定位,Nav1.2在小鼠神经元AIS上呈现出较长的分布。此外,AIS可塑性发生时,大鼠神经元AIS上AnkG和Nav1.2的位置都向远端偏移,且长度均变短;而小鼠神经元的AIS却呈现出变长的AnkG和向远端定位的Nav1.2。综上,我们的研究结果表明,大鼠和小鼠的海马神经元可能在动作电位传播速度、AIS上AnkG和Nav1.2分布的模式以及AIS可塑性特性等方面都存在差异,对这两个物种的实验结果进行比较时需要要考虑到上述情况。.

Keywords: Action potential; Axon initial segment; C57BL/6 mice; Plasticity; Sprague-Dawley rats.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Axon Initial Segment* / physiology
  • Axons / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neurons
  • Rats
  • Rats, Sprague-Dawley

Grants and funding

This work was supported by the National Science and Technology Innovation 2030-Major Program of “Brain Science and Brain-Like Research” (2022ZD0211800), National Natural Science Foundation of China General Research Grant (81971679, 21727806, 31771147) and Major Research Grant (91632305, 32088101), Ministry of Science and Technology (2018YFA0507600, 2017YFA0503600), Qidong-PKU SLS Innovation Fund (2016000663), and Fundamental Research Funds for the Central Universities and National Key R&D Program of China (2020AAA0105200). P.Z. was sponsored by the Bayer Investigator Award