Comprehensive Analysis of Tissue Preservation and Recording Quality from Chronic Multielectrode Implants

Multielectrodes have been used with great success to simultaneously record the activity of neuronal populations in awake, behaving animals. In particular, there is great promise in the use of this technique to allow the control of neuroprosthetic devices by human patients. However, it is crucial to fully characterize the tissue response to the chronic implants in animal models ahead of the initiation of human clinical trials. Here we evaluated the effects of unilateral multielectrode implants on the motor cortex of rats weekly recorded for 1–6 months using several histological methods to assess metabolic markers, inflammatory response, immediate-early gene (IEG) expression, cytoskeletal integrity and apoptotic profiles. We also investigated the correlations between each of these features and firing rates, to estimate the impact of post-implant time on neuronal recordings. Overall, limited neuronal loss and glial activation were observed on the implanted sites. Reactivity to enzymatic metabolic markers and IEG expression were not significantly different between implanted and non-implanted hemispheres. Multielectrode recordings remained viable for up to 6 months after implantation, and firing rates correlated well to the histochemical and immunohistochemical markers. Altogether, our results indicate that chronic tungsten multielectrode implants do not substantially alter the histological and functional integrity of target sites in the cerebral cortex.

多电极（Multielectrode）技术已被广泛且成功地应用于同时记录清醒活动状态下动物的神经元集群活动。具体而言，该技术在助力人类患者操控神经假体（neuroprosthetic）设备领域展现出巨大应用潜力。然而，在启动人体临床试验之前，充分阐明动物模型中慢性植入物引发的组织反应，是至关重要的前提。本研究针对术后1至6个月内每周接受记录的大鼠运动皮层，采用多种组织学方法，对代谢标志物、炎症反应、即刻早期基因（immediate-early gene, IEG）表达、细胞骨架完整性以及细胞凋亡特征进行检测，以此评估单侧多电极植入对其造成的影响。本研究同时分析了上述各项特征与神经元放电频率之间的相关性，以量化评估植入后时长对神经元记录效果的影响。整体而言，植入位点仅观察到轻度神经元丢失与胶质细胞激活。植入侧与非植入侧大脑半球的酶代谢标志物反应性以及即刻早期基因表达，均未呈现显著差异。多电极记录在植入后最长可维持6个月的有效性，且神经元放电频率与组织化学（histochemical）及免疫组织化学（immunohistochemical）标志物具有良好相关性。综合所有实验结果，本研究表明：慢性钨制多电极植入并不会显著改变大脑皮层靶位点的组织学与功能完整性。