Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.
Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.
复制标题
植入大鼠运动皮层的微电极阵列周围的深层锥体神经元的结构和功能变化。
DOI：
10.1016/j.actbio.2023.07.027
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发表时间：
2023
影响因子：
9.7
通讯作者：
Purcell,ErinK
中科院分区：
文献类型：
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作者：
Gregory,BronsonA;Thompson,CortH;Salatino,JosephW;Railing,MiaJ;Zimmerman,ArianaF;Gupta,Bhavna;Williams,Kathleen;Beatty,JosephA;Cox,CharlesL;Purcell,ErinK
能够记录或刺激神经信号的设备为了解正常生理和治疗大脑病理来源创造了新的机会。然而，组织对植入电极的反应可能会影响检测到或刺激的信号的性质。在这项研究中，我们描述了植入大鼠运动皮质的硅基或聚酰亚胺电极周围的深层锥体神经元的结构和功能变化。在植入后1周或6周的时间点收集300微米厚的组织切片，并使用全细胞电生理和双光子成像相结合的方法对单个神经元进行评估。我们观察到设备周围的神经元中树突状树枝被破坏，脊椎密度显著减少。伴随着这些效应的是自发兴奋性突触后电流频率的降低、下垂幅度的降低、峰频率适应的增加和丝足密度的增加。我们假设，在这项研究中观察到的效应可能导致长期植入电极的信号丢失和不稳定。声明意义植入大脑中的电极可以通过记录或刺激局部神经元产生的电信号来治疗病理源和了解正常生理学。然而，植入后的异物反应会破坏这些设备的性能。虽然已经有几项研究通过组织学、转录学和成像来研究设备-组织相互作用的生物学机制，但我们的研究是第一次使用单细胞电生理学直接询问电极周围神经元功能的影响。此外，我们对电极对神经元树突结构和棘细胞形态的影响进行了新的、详细的评估，并评估了传统(硅)和新型聚合物电极材料的影响。这些结果揭示了电极-组织相互作用的新的潜在机制。
Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in deep layer pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 µm-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disrupted dendritic arbors and a significant reduction in spine densities in neurons surrounding devices. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents, a reduction in sag amplitude, an increase in spike frequency adaptation, and an increase in filopodia density. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes.Statement of significanceImplanted electrodes in the brain can be used to treat sources of pathology and understand normal physiology by recording or stimulating electrical signals generated by local neurons. However, a foreign body response following implantation undermines the performance of these devices. While several studies have investigated the biological mechanisms of device-tissue interactions through histology, transcriptomics, and imaging, our study is the first to directly interrogate effects on the function of neurons surrounding electrodes using single-cell electrophysiology. Additionally, we provide new, detailed assessments of the impacts of electrodes on the dendritic structure and spine morphology of neurons, and we assess effects for both traditional (silicon) and newer polymer electrode materials. These results reveal new potential mechanisms of electrode-tissue interactions.