Toloza Enrique H S, Negahbani Ehsan, Fröhlich Flavio
Department of Psychiatry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
J Neurophysiol. 2018 Mar 1;119(3):1029-1036. doi: 10.1152/jn.00541.2017. Epub 2017 Nov 29.
Transcranial current stimulation (tCS) modulates brain dynamics using weak electric fields. Given the pathological changes in brain network oscillations in neurological and psychiatric illnesses, using alternating electric field waveforms that engage rhythmic activity has been proposed as a targeted, network-level treatment approach. Previous studies have investigated the effects of electric fields at the neuronal level. However, the biophysical basis of the cellular response to electric fields has remained limited. Here, we characterized the frequency-dependent response of different compartments in a layer V pyramidal neuron to exogenous electric fields to dissect the relative contributions of voltage-gated ion channels and neuronal morphology. Hyperpolarization-activated cation current (I) in the distal dendrites was the primary ionic mechanism shaping the model's response to electric field stimulation and caused subthreshold resonance in the tuft at 20 ± 4 Hz. In contrast, subthreshold I-mediated resonance in response to local sinusoidal current injection was present in all model compartments at 11 ± 2 Hz. The frequencies of both resonance responses were modulated by I conductance density. We found that the difference in resonance frequency between the two stimulation types can be explained by the fact that exogenous electric fields simultaneously polarize the membrane potentials at the distal ends of the neuron (relative to field direction) in opposite directions. Our results highlight the role of I in shaping the cellular response to electric field stimulation and suggest that the common model of tCS as a weak somatic current injection fails to capture the cellular effects of electric field stimulation. NEW & NOTEWORTHY Modulation of cortical oscillation by brain stimulation serves as a tool to understand the causal role of network oscillations in behavior and is a potential treatment modality that engages impaired network oscillations in disorders of the central nervous system. To develop targeted stimulation paradigms, cellular-level effects must be understood. We demonstrate that hyperpolarization-activated cation current (I) and cell morphology cooperatively shape the response to applied alternating electric fields.
经颅电流刺激（tCS）利用弱电场调节脑动力学。鉴于神经和精神疾病中脑网络振荡的病理变化，使用能够引发节律性活动的交变电场波形已被提议作为一种靶向的、网络水平的治疗方法。先前的研究已经在神经元水平上研究了电场的作用。然而，细胞对电场反应的生物物理基础仍然有限。在这里，我们表征了V层锥体神经元中不同区室对外源性电场的频率依赖性反应，以剖析电压门控离子通道和神经元形态的相对贡献。远端树突中的超极化激活阳离子电流（Ih）是塑造模型对电场刺激反应的主要离子机制，并在20±4Hz时在树突簇中引起阈下共振。相比之下，在11±2Hz时，所有模型区室中都存在对局部正弦电流注入的阈下Ih介导的共振。两种共振反应的频率都受Ih电导密度的调节。我们发现，两种刺激类型之间共振频率的差异可以通过以下事实来解释：外源性电场同时使神经元远端的膜电位（相对于场方向）沿相反方向极化。我们的结果突出了Ih在塑造细胞对电场刺激反应中的作用，并表明将tCS视为弱体电流注入的常见模型未能捕捉到电场刺激的细胞效应。
脑刺激对皮层振荡的调节作为一种工具，有助于理解网络振荡在行为中的因果作用，并且是一种潜在的治疗方式，可用于调节中枢神经系统疾病中受损了的网络振荡。为了开发靶向刺激范式，必须了解细胞水平的效应。我们证明，超极化激活阳离子电流（Ih）和细胞形态共同塑造了对施加的交变电场的反应。
