Department of Biomedical Engineering, The University of Texas at Austin, United States; Department of Physics, The University of Texas at Austin, United States.
Department of Biomedical Engineering, The University of Texas at Austin, United States.
J Neurosci Methods. 2018 Feb 1;295:68-76. doi: 10.1016/j.jneumeth.2017.12.001. Epub 2017 Dec 5.
Despite significant advancements of optical imaging techniques for mapping hemodynamics in small animal models, it remains challenging to combine imaging with spatially resolved electrical recording of individual neurons especially for longitudinal studies. This is largely due to the strong invasiveness to the living brain from the penetrating electrodes and their limited compatibility with longitudinal imaging.
We implant arrays of ultraflexible nanoelectronic threads (NETs) in mice for neural recording both at the brain surface and intracortically, which maintain great tissue compatibility chronically. By mounting a cranial window atop of the NET arrays that allows for chronic optical access, we establish a multimodal platform that combines spatially resolved electrical recording of neural activity and laser speckle contrast imaging (LSCI) of cerebral blood flow (CBF) for longitudinal studies.
We induce peri-infarct depolarizations (PIDs) by targeted photothrombosis, and show the ability to detect its occurrence and propagation through spatiotemporal variations in both extracellular potentials and CBF. We also demonstrate chronic tracking of single-unit neural activity and CBF over days after photothrombosis, from which we observe reperfusion and increased firing rates.
COMPARISON WITH EXISTING METHOD(S): This multimodal platform enables simultaneous mapping of neural activity and hemodynamic parameters at the microscale for quantitative, longitudinal comparisons with minimal perturbation to the baseline neurophysiology.
The ability to spatiotemporally resolve and chronically track CBF and neural electrical activity in the same living brain region has broad applications for studying the interplay between neural and hemodynamic responses in health and in cerebrovascular and neurological pathologies.
尽管在小动物模型中进行血流动力学的光学成像技术取得了显著进展,但将成像与个体神经元的空间分辨电记录相结合仍然具有挑战性,特别是对于纵向研究而言。这主要是因为穿透电极对活体大脑具有很强的侵入性,并且它们与纵向成像的兼容性有限。
我们在小鼠中植入超柔韧的纳米电子线 (NET) 阵列,用于脑表面和皮质内的神经记录,这些阵列在慢性情况下保持很好的组织相容性。通过在 NET 阵列上方安装一个颅窗,允许进行慢性光学访问,我们建立了一个多模态平台,该平台结合了神经活动的空间分辨电记录和激光散斑对比成像 (LSCI) 的脑血流 (CBF),用于纵向研究。
我们通过靶向光血栓形成诱导了周边去极化 (PID),并通过细胞外电势和 CBF 的时空变化显示出检测其发生和传播的能力。我们还证明了在光血栓形成后数天内对单个单元的神经活动和 CBF 进行慢性跟踪,从中我们观察到再灌注和增加的发射率。
该多模态平台能够以微尺度同时映射神经活动和血液动力学参数,进行定量、纵向比较,同时对基础神经生理学的干扰最小。
在同一活体大脑区域中具有时空分辨率和慢性跟踪 CBF 和神经电活动的能力,广泛应用于研究健康和脑血管及神经病理学中神经和血液动力学反应之间的相互作用。