用于在MHz和GHz频率下检测神经球体中活动依赖性变化的装置
Device for detection of activity-dependent changes in neural spheroids at MHz and GHz frequencies
AI总结：
本研究开发了一种利用接地共面波导阵列在MHz-GHz频率下向3D大鼠皮层神经元球体传递电磁波的装置，结合光遗传学同步检测，首次证实了电磁波通过神经组织的传输具有活动依赖性，为研究神经疾病机制和开发新疗法提供了新工具。
摘要：
由神经活动触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。这些过程在神经系统疾病中发挥重要作用。大脑刺激的有益效果也可能通过细胞内变化来介导。目前缺乏用于监测活动依赖性细胞内变化的无标记技术。频率大于1x10^6 Hz (1 MHz)的电磁 (EM) 波此前被用于探测细胞的细胞内内容物，因为在该频率范围内细胞膜变得透明。在MHz-GHz范围内，EM波与细胞内细胞器的膜、蛋白质和水相互作用。在这项工作中，我们开发了一种装置，用于探测活跃神经元的细胞内内容物与EM波之间的相互作用。该装置使用接地共面波导 (GCPWs) 阵列将EM波传递到大鼠皮层神经元的三维 (3D) 球体中。使用光遗传学诱发神经活动，并同步检测EM波的传播。在MHz-GHz范围内进行宽带测量，以跟踪传输系数的变化。研究发现，神经元活动可逆地改变EM波传输。神经元活动的药理学抑制消除了传输中的变化。传输变化的时间常数在几秒到几十秒的范围内，表明存在相对缓慢的、活动依赖性的细胞内过程。本研究提供了EM波通过神经组织的传输在MHz-GHz范围内具有活动依赖性的首个证据。本工作中开发的装置未来可能应用于神经系统疾病机制的研究和新疗法的开发。
英文摘要：
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 1x10^6 Hz (1 MHz) were previously used to probe intracellular contents of cells, as cell membrane becomes transparent 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 intracellular contents of active neurons 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 range of seconds to tens of seconds, 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.
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