Optogenetic interrogation of neurovascular coupling in the cerebral cortex of transgenic mice
Optogenetic interrogation of neurovascular coupling in the cerebral cortex of transgenic mice
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DOI：
10.1088/1741-2552/aad840
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发表时间：
2018-10-01
影响因子：
4
通讯作者：
Pashaie, Ramin
中科院分区：
文献类型：
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作者：
Atry, Farid;Chen, Rex Chin-Hao;Pashaie, Ramin
objective.我们介绍了一种工程方法来研究开环和闭环范例中血管动力学和附近神经活动之间的时空相关性。approach.我们将光遗传学技术与光学相干断层扫描技术相结合，将光学神经刺激的时空模式应用于转基因光遗传学小鼠的皮层，并测量选定的大脑中动脉分支的血流速率、速度和直径变化。主要结果。测量局部神经刺激光脉冲的血流速率、速度和血管直径响应的时空特征。据观察，刺激相对于周围血管拓扑结构的位置对血管动力学反应的时间模式有显著影响。通过创建选定动脉的速度、流速和直径灵敏度图来研究这种效应。一般来说，在动脉下游毛细血管附近的神经刺激诱发血液流速、速度和血管直径的快速瞬时增加，随后是持久的次级峰值反应。流速反应的时间跨度与刺激的长度成准线性比例。当神经刺激传递到动脉的一个子分支附近的区域时，在其他分支中，我们观察到血液速度和/或流速的一些下降以及血管直径的同时增加。为了检查神经活动和局部血流之间的耦合的可靠性，实现了闭环反馈控制器，其能够通过连续地调节刺激脉冲的宽度来将血流速率维持在任何期望的水平相对较长的时间段。意义所提出的方法开辟了新的研究领域，在了解不同类型的细胞在脑血管调节机制中的作用和研究大脑皮层血管生成的自适应过程中具有潜在的应用。对血管直径、血流速率和速度的不相干响应的观察表明，这种详细信息对于获得通过基于血流动力学的功能成像技术获得的数据的准确解释是必要的。
Objective. We introduce an engineering approach to study spatiotemporal correlations between vasodynamics and the nearby neural activity in open-loop and closed-loop paradigms. Approach. We integrated optogenetic technology with optical coherence tomography to apply spatiotemporal patterns of optical neurostimulation to the cortex of transgenic optogenetic mice and measure blood flow-rate, velocity, and diameter changes of selected middle cerebral artery branches. Main results. The spatiotemporal characteristics of blood flow-rate, velocity, and vessel diameter responses to localized neurostimulation light pulses were measured. It was observed that the location of stimulation relative to the surrounding vascular topology had notable effects on temporal patterns of vasodynamic responses. This effect was studied by creating velocity, flow-rate, and diameter sensitivity maps for selected arteries. Generally, neural stimulation in the vicinity of downstream capillaries of an artery evoked a fast transient increase in the blood flow-rate, velocity, and vessel diameter which was followed by a long-lasting secondary peak-response. The temporal span of the flow-rate response was quasi-linearly proportional to the length of stimulation. When neural stimulation was delivered to the area in the vicinity of one daughter branch of an artery, in other branches, we observed some drop in blood velocity and/or flow-rate and concurring increase of the vessel diameter. To examine the reliability of the coupling between neural activity and regional blood flow, a closed-loop feedback controller was implemented which is capable of maintaining blood flow-rate at any desired level for relatively longer periods by continuously adjusting the width of stimulation pulses. Significance. The proposed approach opens new lines of research with potential applications in understanding the role of different cell types in the cerebrovascular regulatory mechanisms and the study of the adaptive process of angiogenesis in the cerebral cortex. The observation of incoherent responses of vessel diameter, blood flow-rate, and velocity suggests that such detailed information is necessary to obtain an accurate interpretation of the data acquired via hemodynamic based functional imaging techniques.