Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States of America. Harvard-MIT Health Sciences and Technology Division, Massachusetts Institute of Technology, Cambridge, MA 02139, United States of America. These authors contributed equally to this work.
J Neural Eng. 2020 Jul 24;17(4):044001. doi: 10.1088/1741-2552/aba161.
The vast majority of techniques to study the physiology of the nervous system involve inserting probes into the brain for stimulation, recording, or sampling. Research is increasingly uncovering the fine microstructure of the brain, each of its regions with dedicated functions. Accurate knowledge of the placement of probes interrogating these regions is critical. We have developed a customizable concentric marking electrode (CME) consisting of an iron core within a 125 μm-stainless steel (SS) sheath for co-localization of targeted regions in the brain. We used a dielectric layer stack of SiO, AlO, SiO to electrically encapsulate the iron core and minimize exposure area to avoid significant increases in inflammatory response triggered by the probes. The CME can record multi-neuronal extracellular firing patterns. Appropriate electrical polarity of the iron and SS components controls the deposition of iron microdeposits on brain tissue. We show that in vivo labels by this method can be as small as 100 μm, visible via noninvasive magnetic resonance imaging (MRI) as well as post-mortem histology, and illustrate how deposit size can be tuned by varying stimulus parameters. We targeted the CA3 area of the hippocampus in adult rats and demonstrate that iron microdeposits are remarkably stable and persist up to 10 months post-deposition. Using a single probe for recording and marking avoids inaccuracies with re-insertion of separate probes and utilizes iron microdeposits as valuable fiducial markers in vivo and ex vivo.
绝大多数研究神经系统生理学的技术都涉及将探针插入大脑进行刺激、记录或采样。研究越来越多地揭示了大脑的精细微观结构，每个区域都有特定的功能。准确了解用于探查这些区域的探针的位置至关重要。我们开发了一种可定制的同心标记电极 (CME)，它由铁核和 125μm 不锈钢 (SS) 护套组成，用于大脑中靶向区域的共定位。我们使用 SiO、AlO、SiO 介电层堆栈来电封装铁核并最小化暴露面积，以避免探针引发的炎症反应显著增加。CME 可以记录多神经元细胞外放电模式。铁和 SS 组件的适当电极极性控制着铁微沉积物在脑组织上的沉积。我们表明，通过这种方法进行的体内标记可以小至 100μm，通过非侵入性磁共振成像 (MRI) 以及死后组织学可见，并说明了如何通过改变刺激参数来调整沉积物的大小。我们以成年大鼠的海马 CA3 区为目标，证明铁微沉积物非常稳定，在沉积后长达 10 个月内都能保持稳定。使用单个探针进行记录和标记可以避免因重新插入单独的探针而导致的不准确，并将铁微沉积物用作体内和体外有价值的基准标记物。
