Optically transparent neural microelectrodes have facilitated simultaneous electrophysiological recordings from the brain surface with the optical imaging and stimulation of neural activity. A remaining challenge is to scale down the electrode dimensions to the single-cell size and increase the density to record neural activity with high spatial resolution across large areas to capture nonlinear neural dynamics. Here we developed transparent graphene microelectrodes with ultrasmall openings and a large, transparent recording area without any gold extensions in the field of view with high-density microelectrode arrays up to 256 channels. We used platinum nanoparticles to overcome the quantum capacitance limit of graphene and to scale down the microelectrode diameter to 20 µm. An interlayer-doped double-layer graphene was introduced to prevent open-circuit failures. We conducted multimodal experiments, combining the recordings of cortical potentials of microelectrode arrays with two-photon calcium imaging of the mouse visual cortex. Our results revealed that visually evoked responses are spatially localized for high-frequency bands, particularly for the multiunit activity band. The multiunit activity power was found to be correlated with cellular calcium activity. Leveraging this, we employed dimensionality reduction techniques and neural networks to demonstrate that single-cell and average calcium activities can be decoded from surface potentials recorded by high-density transparent graphene arrays.

光学透明的神经微电极促进了大脑表面电生理学记录与光学成像和神经活动刺激的同时进行。剩下的挑战是将电极尺寸缩小到单细胞大小并增加密度，以在大面积上以高空间分辨率记录神经活动，以捕获非线性神经动力学。在这里，我们开发了透明石墨烯微电极，具有超小开口和大的透明记录区域，视野中没有任何金延伸，具有高达 256 个通道的高密度微电极阵列。我们使用铂纳米粒子来克服石墨烯的量子电容限制，并将微电极直径缩小至 20 µm。引入层间掺杂双层石墨烯来防止开路故障。我们进行了多模态实验，将微电极阵列的皮层电位记录与小鼠视觉皮层的双光子钙成像相结合。我们的结果表明，视觉诱发反应在高频带上是空间局部化的，特别是对于多单元活动频带。发现多单位活动功率与细胞钙活性相关。利用这一点，我们采用降维技术和神经网络来证明单细胞和平均钙活动可以从高密度透明石墨烯阵列记录的表面电位解码。