Optical Probes for Neurobiological Sensing and Imaging.

Optical Probes for Neurobiological Sensing and Imaging.
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DOI:
10.1021/acs.accounts.7b00564
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发表时间:
2018-05-15
影响因子:
18.3
通讯作者:
Clark HA
Clark HA
中科院分区:
化学1区
文献类型:
--
作者:
Kim EH;Chin G;Rong G;Poskanzer KE;Clark HA

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荧光纳米传感器和分子探针是用于成像细胞内和细胞间化学信号的下一代工具。电生理学一直被认为是阐明神经动力学的黄金标准,具有高的时间分辨率和精度,特别是在单细胞水平上。然而,基于电极的技术面临的挑战,照亮特定的化学物质参与神经细胞激活与足够的空间信息。测量化学动力学对于更好地理解神经元之间的协同相互作用以及神经元和非神经元细胞之间的相互作用具有根本重要性。在过去的十年里,光学探针和成像方法的重大技术进步为在化学水平上研究神经细胞和电路提供了全新的可能性。这些光学成像模式已经显示出结合化学、时间和空间信息的前景。这种潜力使它们成为解开大脑中多个尺度上复杂神经相互作用的理想候选人,这可以通过传统的电生理方法来补充,以获得神经化学动力学的完整时空图像。尽管有潜力,但只有少数候选探针被用于提供大脑中的详细化学信息。迄今为止,大多数实时成像和化学作图研究依赖于荧光分子指示剂来报告与神经元活动相关的细胞内钙(Ca2+)动态。因此,通过提高空间、时间和化学分辨率来监测大脑中一系列化学物质的方法学进步将使神经化学回路的映射具有更高的精度。在这个令人兴奋的领域的众多研究的基础上,我们回顾了目前的努力,开发和应用的光学探针和纳米传感器的调色板在大脑中的化学传感。有一个强大的推动力,进一步发展技术,能够探测整个神经生物学单位与高时空分辨率。因此,我们介绍了离子和神经递质检测研究神经元和非神经元脑细胞的选定应用程序。我们专注于光学探针的家庭,因为它们能够感测广泛的分子阵列,并传达空间信息,对组织的损伤最小。我们从讨论目前可用的分子探针开始,突出了离子和小分子的转基因荧光探针的最新进展,并以生物成像纳米传感器的最新研究结束。可定制的纳米级光学传感器可以准确和动态地监测局部环境,具有高时空分辨率,不仅可以对所有细胞类型的功能产生新的见解,还可以更广泛地了解不同的神经信号系统如何以空间相关的方式与相邻细胞一起发挥作用。
Fluorescent nanosensors and molecular probes are next-generation tools for imaging chemical signaling inside and between cells. Electrophysiology has long been considered the gold standard in elucidating neural dynamics with high temporal resolution and precision, particularly on the single-cell level. However, electrode-based techniques face challenges in illuminating the specific chemicals involved in neural cell activation with adequate spatial information. Measuring chemical dynamics is of fundamental importance to better understand synergistic interactions between neurons as well as interactions between neurons and non-neuronal cells. Over the past decade, significant technological advances in optical probes and imaging methods have enabled entirely new possibilities for studying neural cells and circuits at the chemical level. These optical imaging modalities have shown promise for combining chemical, temporal, and spatial information. This potential makes them ideal candidates to unravel the complex neural interactions at multiple scales in the brain, which could be complemented by traditional electrophysiological methods to obtain a full spatiotemporal picture of neurochemical dynamics. Despite the potential, only a handful of probe candidates have been utilized to provide detailed chemical information in the brain. To date, most live imaging and chemical mapping studies rely on fluorescent molecular indicators to report intracellular calcium (Ca2+) dynamics, which correlates with neuronal activity. Methodological advances for monitoring a full array of chemicals in the brain with improved spatial, temporal, and chemical resolution will thus enable mapping of neurochemical circuits with finer precision. On the basis of numerous studies in this exciting field, we review the current efforts to develop and apply a palette of optical probes and nanosensors for chemical sensing in the brain. There is a strong impetus to further develop technologies capable of probing entire neurobiological units with high spatiotemporal resolution. Thus, we introduce selected applications for ion and neurotransmitter detection to investigate both neurons and non-neuronal brain cells. We focus on families of optical probes because of their ability to sense a wide array of molecules and convey spatial information with minimal damage to tissue. We start with a discussion of currently available molecular probes, highlight recent advances in genetically modified fluorescent probes for ions and small molecules, and end with the latest research in nanosensors for biological imaging. Customizable, nanoscale optical sensors that accurately and dynamically monitor the local environment with high spatiotemporal resolution could lead to not only new insights into the function of all cell types but also a broader understanding of how diverse neural signaling systems act in conjunction with neighboring cells in a spatially relevant manner.
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