Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
Department of Biomedical Engineering, The City College of New York of CUNY, New York, NY, USA.
Cereb Cortex. 2018 Aug 1;28(8):2786-2794. doi: 10.1093/cercor/bhx158.
Understanding which cellular compartments are influenced during neuromodulation underpins any rational effort to explain and optimize outcomes. Axon terminals have long been speculated to be sensitive to polarization, but experimentally informed models for CNS stimulation are lacking. We conducted simultaneous intracellular recording from the neuron soma and axon terminal (blebs) during extracellular stimulation with weak sustained (DC) uniform electric fields in mouse cortical slices. Use of weak direct current stimulation (DCS) allowed isolation and quantification of changes in axon terminal biophysics, relevant to both suprathreshold (e.g., deep brain stimulation, spinal cord stimulation, and transcranial magnetic stimulation) and subthreshold (e.g., transcranial DCS and transcranial alternating current stimulation) neuromodulation approaches. Axon terminals polarized with sensitivity (mV of membrane polarization per V/m electric field) 4 times than somas. Even weak polarization (<2 mV) of axon terminals significantly changes action potential dynamics (including amplitude, duration, conduction velocity) in response to an intracellular pulse. Regarding a cellular theory of neuromodulation, we explain how suprathreshold CNS stimulation activates the action potential at terminals while subthreshold approaches modulate synaptic efficacy through axon terminal polarization. We demonstrate that by virtue of axon polarization and resulting changes in action potential dynamics, neuromodulation can influence analog-digital information processing.
理解神经调节过程中哪些细胞区室受到影响，是任何解释和优化结果的合理努力的基础。轴突末梢长期以来一直被推测对极化敏感，但缺乏针对中枢神经系统刺激的实验性信息模型。我们在小鼠皮质切片中进行了细胞外弱持续（DC）均匀电场刺激时神经元胞体和轴突末梢（blebs）的同时细胞内记录。使用弱直流刺激（DCS）允许分离和量化轴突末梢生物物理学的变化，这与阈上（例如，深部脑刺激、脊髓刺激和经颅磁刺激）和阈下（例如，经颅 DCS 和经颅交流电刺激）神经调节方法都相关。轴突末梢的极化灵敏度（mV/m 电场的膜极化 mV）比胞体高 4 倍。即使是轴突末梢的弱极化（<2 mV）也会显著改变动作电位动力学（包括幅度、持续时间、传导速度）对细胞内脉冲的反应。关于神经调节的细胞理论，我们解释了阈上中枢神经系统刺激如何在末梢激活动作电位，而阈下方法如何通过轴突末梢极化来调节突触效能。我们证明，由于轴突极化和动作电位动力学的变化，神经调节可以影响模拟-数字信息处理。
