Xia Mingyi, Agca Busra Nur, Yoshida Tomoko, Choi Jiwon, Amjad Usamma, Bose Kade, Keren Nikol, Zukerman Shahar, Cima Michael J, Graybiel Ann M, Schwerdt Helen N
McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA.
Department of Bioengineering, University of Pittsburgh, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
Biosens Bioelectron. 2023 Dec 1;241:115625. doi: 10.1016/j.bios.2023.115625. Epub 2023 Aug 21.
We developed a flexible "electrode-thread" array for recording dopamine neurochemicals from a lateral distribution of subcortical targets (up to 16) transverse to the axis of insertion. Ultrathin (∼10 μm diameter) carbon fiber (CF) electrode-threads (CFETs) are clustered into a tight bundle to introduce them into the brain from a single-entry point. The individual CFETs splay laterally in deep brain tissue during insertion due to their innate flexibility. This spatial redistribution allows navigation of the CFETs towards deep brain targets spreading horizontally from the axis of insertion. Commercial "linear" arrays provide single-entry insertion but only allow measurements along the axis of insertion. Horizontally configured arrays inflict separate penetrations for each individual channel. We tested functional performance of our CFET arrays in vivo for recording dopamine and for providing lateral spread to multiple distributed sites in the rat striatum. Spatial spread was further characterized in agar brain phantoms as a function of insertion depth. We also developed protocols to slice the embedded CFETs within fixed brain tissue using standard histology. This method allowed extraction of the precise spatial coordinates of the implanted CFETs and their recording sites as integrated with immunohistochemical staining for surrounding anatomical, cytological, and protein expression labels. Our CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinson's disease and major mood disorders.
我们开发了一种灵活的“电极线”阵列，用于从与插入轴横向的皮质下靶点（最多16个）的侧向分布中记录多巴胺神经化学物质。超薄（直径约10μm）碳纤维（CF）电极线（CFET）聚集在一起形成紧密束状，以便从单个入口点将它们引入大脑。由于其固有的柔韧性，单个CFET在插入过程中会在深部脑组织中横向展开。这种空间重新分布使得CFET能够朝向从插入轴水平延伸的深部脑靶点导航。商业“线性”阵列提供单入口插入，但仅允许沿插入轴进行测量。水平配置的阵列对每个单独通道进行单独穿刺。我们在体内测试了CFET阵列记录多巴胺以及向大鼠纹状体中多个分布位点提供侧向扩展的功能性能。在琼脂脑模型中进一步表征了作为插入深度函数的空间扩展。我们还开发了使用标准组织学在固定脑组织内切片嵌入的CFET的方案。这种方法允许提取植入的CFET及其记录位点的精确空间坐标，以及与周围解剖、细胞学和蛋白质表达标记的免疫组织化学染色相结合。我们的CFET阵列有可能开启广泛的应用，从揭示神经调节剂在突触可塑性中的作用，到解决帕金森病和主要情绪障碍临床转化为诊断和适应性治疗过程中的关键安全障碍。
