Department of Bioengineering, Lehigh University, Bethlehem, USA.
Department of Material Science and Engineering, Cornell University, Ithaca, USA.
Biosens Bioelectron. 2025 Jan 1;267:116816. doi: 10.1016/j.bios.2024.116816. Epub 2024 Sep 25.
Intracellular processes triggered by neural activity include changes in ionic concentrations, protein release, and synaptic vesicle cycling. These processes play significant roles in neurological disorders. The beneficial effects of brain stimulation may also be mediated through intracellular changes. There is a lack of label-free techniques for monitoring activity-dependent intracellular changes. Electromagnetic (EM) waves at frequencies larger than 1 × 10 Hz (1 MHz) were previously used to probe intracellular contents of cells, as cell membrane becomes "invisible" at this frequency range. EM waves interact with membranes of intracellular organelles, proteins, and water in the MHz - GHz range. In this work, we developed a device for probing the interaction between active neurons' intracellular contents and EM waves. The device used an array of grounded coplanar waveguides (GCPWs) to deliver EM waves to a three-dimensional (3D) spheroid of rat cortical neurons. Neural activity was evoked using optogenetics, with synchronous detection of propagation of EM waves. Broadband measurements were conducted in the MHz-GHz range to track changes in transmission coefficients. Neuronal activity was found to reversibly alter EM wave transmission. Pharmacological suppression of neuronal activity abolished changes in transmission. Time constants of changes in transmission were in the seconds - tens of seconds range, suggesting the presence of relatively slow, activity-dependent intracellular processes. This study provides the first evidence that EM transmission through neuronal tissue is activity-dependent in MHz - GHz range. Device developed in this work may find future applications in studies of the mechanisms of neurological disorders and the development of new therapies.
神经活动引发的细胞内过程包括离子浓度变化、蛋白质释放和突触囊泡循环。这些过程在神经紊乱中发挥重要作用。脑刺激的有益效果也可能通过细胞内变化来介导。目前还缺乏用于监测活动依赖性细胞内变化的无标记技术。先前，频率大于 1×10 Hz（1 MHz）的电磁波被用于探测细胞的细胞内内容物，因为细胞膜在此频率范围内变得“不可见”。电磁波在兆赫兹到千兆赫兹范围内与细胞内细胞器、蛋白质和水的细胞膜相互作用。在这项工作中，我们开发了一种用于探测活跃神经元细胞内内容物与电磁波相互作用的设备。该设备使用接地共面波导（GCPW）阵列将电磁波传输到大鼠皮质神经元的三维（3D）球体。使用光遗传学来诱发神经活动，并同步检测电磁波的传播。在兆赫兹到千兆赫兹范围内进行宽带测量以跟踪传输系数的变化。发现神经元活动可可逆地改变电磁波的传输。神经元活动的药理学抑制消除了传输的变化。传输变化的时间常数在秒到数十秒的范围内，表明存在相对较慢的、活动依赖性的细胞内过程。这项研究首次提供了证据，表明在兆赫兹到千兆赫兹范围内，通过神经元组织的电磁波传输是活动依赖性的。这项工作中开发的设备可能会在神经紊乱机制研究和新疗法的开发中找到未来的应用。
