Pioneers in Neurophotonics: Special Section Honoring Professor Lawrence B. Cohen.
Pioneers in Neurophotonics: Special Section Honoring Professor Lawrence B. Cohen.
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神经光子学先驱：劳伦斯·B·科恩教授特别部分。
DOI：
10.1117/1.nph.2.2.021001
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发表时间：
2015
期刊：
影响因子：
5.3
通讯作者：
Zecevic,Dejan
中科院分区：
文献类型：
--
作者：
Salzberg,BrianM;Zecevic,Dejan
Larry Cohen在20世纪60年代后期开始探索膜功能（光散射和双折射）的光学方法，当时他还是Richard D.凯恩斯在剑桥大学。在接下来的40年里，科恩成为细胞生理学、生物物理学和神经科学中光学方法的发展和应用的主导人物。事实上，目前涉及光子测量的无数技术中的大多数都可以追溯到科恩的直接发起或他的积极参与。从20世纪70年代初开始，拉里·科恩（Larry Cohen）开始使用电压钳制的鱿鱼巨型轴突来筛选数千种物质，首先是荧光物质，然后仅仅是有色物质，因为它们对电压敏感，没有光毒性。1972年，劳伦斯·科恩和合作者发现，Mercury 540是第一个敏感的膜电位分子指示剂（电位染料），可用于记录鱿鱼巨轴突的动作电位，而无需平均。1973年，科恩和他的同事再次使用Mercury 540监测了单个水蛭感觉神经元的电活动，这是第一个来自真实的完整神经元的光学记录。然后，在1977年，科恩的实验室表明，多达14个藤壶神经元可以同时监测，并单独使用电压敏感的吸收染料。兴奋性和抑制性的动作电位和突触电位可以记录许多秒。这开启了同时从许多神经元进行光学记录的时代，最终记录了数百个神经元，这些神经元来自无脊椎动物的神经节和哺乳动物的皮质。这一时期的许多亮点之一是证明无脊椎动物的简单学习范式涉及数百个神经元的参与。在近40年的时间里，已经合成和分析了数千种可能的电位探针，在过去的十年里，拉里一直处于探索遗传编码的电压敏感蛋白质的最前沿。这些分子中的绝大多数在光谱的可见光区域吸收和发射，并且许多在细胞和组织生理学的研究中发现了广泛的应用。现在，电压敏感染料的光谱范围已远远扩展到红色，并将很快扩展到红外线。这些分子探针不仅允许它们在对可见光中的光子敏感的视网膜等组织中使用，而且更长波长的激发和发射将能够增强光在心脏和大脑等三维结构中的穿透，其中活动的时空模式既不简单也不总是肤浅的。最早提出的电压敏感染料的应用之一是它们在探测细胞的其他不可接近区域的膜电压中的潜在用途，也许最好的例子是骨骼肌的横管系统。这些很快就被实现了，因为这些分子电压表有更多的用途。从动态电场的分子内分析到大脑活动的皮层和皮层下映射，科恩教授的工作和影响，特别是膜电位的光学记录和细胞生理学中的光学方法，给我们所有人带来了启发。就个人而言，拉里有着非凡的思维敏捷和分析能力。这往往被他说话的缓慢所掩盖，这通常反映了考虑和谨慎。他还表现出不寻常的天赋，认识到重要的突出问题，在他的兴趣领域，以及在其他领域。因此，他通常远远领先于他的领域...
Larry Cohen began to explore optical approaches to membrane function (light scattering and birefringence) in the late 1960s when he was still a postdoctoral fellow in the laboratory of Richard D. Keynes at the University of Cambridge. During the next forty years, Cohen became the dominant figure in developing and applying optical methods in cell physiology, biophysics, and neuroscience. Indeed, most of the myriad current techniques involving photonic measurements can be traced to Cohen’s direct initiation or his active involvement. Beginning in the early 1970s, Larry Cohen began using voltage-clamped squid giant axons to screen literally thousands of substances, first fluorescent, and then merely colored, for their voltage sensitivity and freedom from phototoxicity. In 1972, Lawrence Cohen and collaborators showed that Merocyanine 540, the first sensitive molecular indicator of membrane potential (potentiometric dye), could be used to record the action potential, without averaging, from squid giant axons. In 1973, again using Merocyanine 540, Cohen and colleagues monitored electrical activity from an individual leech sensory neuron, and this was the first optical recording from a real intact neuron. Then, in 1977, Cohen’s lab showed that as many as fourteen barnacle neurons could be monitored simultaneously, and individually, using voltage-sensitive absorbance dyes. Action potentials and synaptic potentials, both excitatory and inhibitory, could be recorded for many seconds. This began the era of optical recording from many neurons simultaneously, culminating in the recording of hundreds of neurons from preparations as diverse as invertebrate ganglia and mammalian cortices. Among many highlights from this period was the demonstration that simple learning paradigms in invertebrates involved the participation of hundreds of neurons. In nearly four decades, several thousand plausibly potentiometric probes have been synthesized and assayed, and, in the last decade, Larry has been in the forefront of exploring genetically encoded voltage-sensitive proteins. The vast majority of these molecules absorb and emit in the visible region of the spectrum and many have found wide application in studies of cell and tissue physiology. Now, the spectral range of voltage-sensitive dyes has been extended far into the red and will soon be extended into the infra-red. Not only will these molecular probes permit their use in tissues like the retina that are sensitive to photons in the visible, but longer wavelength excitation and emission will enable enhanced light penetration in three-dimensional structures like the heart and brain, where the spatiotemporal patterns of activity are neither simple nor always superficial. Among the earliest suggested applications of voltage-sensitive dyes was their potential use in probing membrane voltage at otherwise inaccessible regions of cells, perhaps best exemplified by the transverse tubular system of skeletal muscle. These were quickly realized, as were many more uses for these molecular voltmeters. From intramolecular profiling of the dynamic electric field to cortical and subcortical mapping of brain activity, Prof. Cohen’s work and influence on optical recording of membrane potential in particular and optical methods in cell physiology in general have enlightened us all. More personally, Larry has a remarkable quickness of mind and analytical ability. This is often belied by his slowness of speech, which usually reflects consideration and caution. He also evinces unusual talent for recognizing important outstanding problems in his area of interest, and in other areas as well. As a result, he is usually far in advance of his field …