Ronchi Silvia, Fiscella Michele, Marchetti Camilla, Viswam Vijay, Müller Jan, Frey Urs, Hierlemann Andreas
Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
MaxWell Biosystems AG, Basel, Switzerland.
Front Neurosci. 2019 Mar 13;13:208. doi: 10.3389/fnins.2019.00208. eCollection 2019.
Non-invasive electrical stimulation can be used to study and control neural activity in the brain or to alleviate somatosensory dysfunctions. One intriguing prospect is to precisely stimulate individual targeted neurons. Here, we investigated single-neuron current and voltage stimulation using high-density microelectrode arrays featuring 26,400 bidirectional electrodes at a pitch of 17.5 μm and an electrode area of 5 × 9 μm. We determined optimal waveforms, amplitudes and durations for both stimulation modes. Owing to the high spatial resolution of our arrays and the close proximity of the electrodes to the respective neurons, we were able to stimulate the axon initial segments (AIS) with charges of less than 2 pC. This resulted in minimal artifact production and reliable readout of stimulation efficiency directly at the soma of the stimulated cell. Stimulation signals as low as 70 mV or 100 nA, with pulse durations as short as 18 μs, yielded measurable action potential initiation and propagation. We found that the required stimulation signal amplitudes decreased with cell growth and development and that stimulation efficiency did not improve at higher electric fields generated by simultaneous multi-electrode stimulation.
非侵入性电刺激可用于研究和控制大脑中的神经活动，或缓解体感功能障碍。一个有趣的前景是精确刺激单个目标神经元。在此，我们使用了高密度微电极阵列来研究单神经元电流和电压刺激，该阵列具有26400个双向电极，电极间距为17.5μm，电极面积为5×9μm。我们确定了两种刺激模式的最佳波形、幅度和持续时间。由于我们阵列的高空间分辨率以及电极与各个神经元的紧密接近程度，我们能够以小于2 pC的电荷量刺激轴突起始段（AIS）。这导致产生的伪迹最小，并能在被刺激细胞的胞体处直接可靠地读出刺激效率。低至70 mV或100 nA的刺激信号，脉冲持续时间短至18μs，就能产生可测量到的动作电位起始和传播。我们发现所需的刺激信号幅度随着细胞的生长和发育而降低，并且在同时进行多电极刺激产生的更高电场下，刺激效率并未提高。
