Huang Xuelin, Wei Xile, Wang Jiang, Yi Guosheng
School of Electrical and Information Engineering, Tianjin University, Tianjin, 300072, China.
J Comput Neurosci. 2025 Mar;53(1):25-36. doi: 10.1007/s10827-024-00886-y. Epub 2024 Dec 17.
Transcranial direct current stimulation (tDCS) generates a weak electric field (EF) within the brain, which induces opposite polarization in the soma and distal dendrite of cortical pyramidal neurons. The somatic polarization directly affects the spike timing, and dendritic polarization modulates the synaptically evoked dendritic activities. Ca spike, the most dramatic dendritic activity, is crucial for synaptic integration and top-down signal transmission, thereby indirectly influencing the output spikes of pyramidal cells. Nevertheless, the role of dendritic Ca spike in the modulation of neural spike timing with tDCS remains largely unclear. In this study, we use morphologically and biophysically realistic models of layer 5 pyramidal cells (L5 PCs) to simulate the dendritic Ca spike and somatic Na spike in response to distal dendritic synaptic inputs under weak EF stimulation. Our results show that weak EFs modulate the spike timing through the modulation of dendritic Ca spike and somatic polarization, and such field effects are dependent on synaptic inputs. At weak synaptic inputs, the spike timing is advanced due to the facilitation of dendritic Ca spike by field-induced dendritic depolarization. Conversely, it is delayed by field-induced dendritic hyperpolarization. In this context, the Ca spike exhibits heightened sensitivity to weak EFs, thereby governing the changes in spike timing. At strong synaptic inputs, somatic polarization dominates the changes in spike timing due to the decreased sensitivity of Ca spike to EFs. Consequently, the spike timing is advanced/delayed by field-induced somatic depolarization/hyperpolarization. Moreover, EFs have significant effects on the changes in the timing of somatic spike and Ca spike when synaptic current injection coincides with the onset of EFs. Field effects on spike timing follow a cosine dependency on the field polar angle, with maximum effects in the field direction parallel to the somato-dendritic axis. Furthermore, our results are robust to morphological and biological diversity. These findings clarify the modulation of spike timing with weak EFs and highlight the crucial role of dendritic Ca spike. These predictions shed light on the neural basis of tDCS and should be considered when understanding the effect of tDCS on population dynamics and cognitive behavior.
经颅直流电刺激(tDCS)在大脑内产生一个弱电场(EF),该电场在皮质锥体神经元的胞体和远端树突中诱导相反的极化。胞体极化直接影响动作电位发放时间,而树突极化则调节突触诱发的树突活动。钙离子动作电位是最显著的树突活动,对突触整合和自上而下的信号传递至关重要,从而间接影响锥体细胞的输出动作电位。然而,钙离子动作电位在tDCS调节神经动作电位发放时间中的作用仍 largely 不清楚。在本研究中,我们使用形态学和生物物理学上逼真的第 5 层锥体细胞(L5 PCs)模型,来模拟在弱电场刺激下对远端树突突触输入的反应中的树突钙离子动作电位和胞体钠离子动作电位。我们的结果表明,弱电场通过调节树突钙离子动作电位和胞体极化来调节动作电位发放时间,并且这种场效应依赖于突触输入。在弱突触输入时,由于场诱导的树突去极化促进了树突钙离子动作电位,动作电位发放时间提前。相反,它会因场诱导的树突超极化而延迟。在这种情况下,钙离子动作电位对弱电场表现出更高的敏感性,从而控制动作电位发放时间的变化。在强突触输入时,由于钙离子动作电位对电场的敏感性降低,胞体极化主导动作电位发放时间的变化。因此,动作电位发放时间因场诱导的胞体去极化/超极化而提前/延迟。此外,当突触电流注入与电场开始同时发生时,电场对胞体动作电位和钙离子动作电位的时间变化有显著影响。电场对动作电位发放时间的影响遵循与场极角的余弦依赖性,在场方向平行于胞体 - 树突轴时效果最大。此外,我们的结果对形态学和生物学多样性具有鲁棒性。这些发现阐明了弱电场对动作电位发放时间的调节,并突出了树突钙离子动作电位的关键作用。这些预测揭示了 tDCS 的神经基础,在理解 tDCS 对群体动力学和认知行为的影响时应予以考虑。
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