Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity. Additionally, intracortical microelectrodes have the ability to return function to individuals with paralysis as part of a brain computer interface. Unfortunately, the neural signals recorded by these electrodes degrade over time. Many strategies which target the biological and/or materials mediating failure modes of this decline of function are currently under investigation. The goal of this study is to identify a precise cellular target for future intervention to sustain chronic intracortical microelectrode performance. Previous work from our lab has indicated that the Cluster of Differentiation 14/Toll-like receptor pathway (CD14/TLR) is a viable target to improve chronic laminar, silicon intracortical microelectrode recordings. Here, we use a mouse bone marrow chimera model to selectively knockout CD14, an innate immune receptor, from either brain resident microglia or blood-derived macrophages, in order to understand the most effective targets for future therapeutic options. Using single-unit recordings we demonstrate that inhibiting CD14 from the blood-derived macrophages improves recording quality over the 16 week long study. We conclude that targeting CD14 in blood-derived cells should be part of the strategy to improve the performance of intracortical microelectrodes, and that the daunting task of delivering therapeutics across the blood-brain barrier may not be needed to increase intracortical microelectrode performance.

皮质内微电极为研究人员提供了精确监测神经尖峰活动的有效工具。此外，作为脑机接口的一部分，皮质内微电极能够使瘫痪个体恢复功能。不幸的是，这些电极记录的神经信号会随着时间的推移而减弱。目前正在研究许多针对介导这种功能衰退的失效模式的生物和/或材料的策略。这项研究的目的是确定未来干预的精确细胞靶点，以维持慢性皮质内微电极的性能。我们实验室之前的工作表明，分化簇 14/Toll 样受体通路 (CD14/TLR) 是改善慢性层状硅皮质内微电极记录的可行靶标。在这里，我们使用小鼠骨髓嵌合体模型从大脑驻留的小胶质细胞或血液来源的巨噬细胞中选择性敲除 CD14（一种先天免疫受体），以便了解未来治疗方案的最有效靶标。使用单单元记录，我们证明在为期 16 周的研究中，抑制血液来源巨噬细胞中的 CD14 可提高记录质量。我们的结论是，针对血源性细胞中的 CD14 应该成为提高皮质内微电极性能策略的一部分，并且可能不需要通过血脑屏障传递治疗药物的艰巨任务来提高皮质内微电极的性能。