Advanced Circuit and Cellular Imaging Methods in Nonhuman Primates
Advanced Circuit and Cellular Imaging Methods in Nonhuman Primates
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DOI：
10.1523/jneurosci.1168-19.2019
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发表时间：
2019-10-16
影响因子：
5.3
通讯作者：
Martinez-Conde, Susana
中科院分区：
文献类型：
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作者：
Macknik, Stephen L.;Alexander, Robert G.;Martinez-Conde, Susana
在过去的二十年里，新的遗传编码工具和先进的显微镜方法使昆虫和啮齿动物的神经回路分析发生了革命性的变化。虽然许多技术障碍最初阻止了这些方法在非人类灵长类动物(NHP)上取得成功，但目前的研究已经开始克服这些障碍。在某些情况下，与国家卫生规划一起开发的方法进步甚至超过了它们的前身。其中一项进步包括在NHP皮层上新的超大成像窗口，它比整个啮齿类动物的大脑都大，允许分析前所未有的超大规模电路。NHP成像室现在的专利期限比小鼠的寿命更长，允许在与人类认知发展相关的时间范围内对识别出的电路和神经元进行长期的全光询问。在这里，我们介绍了由研究团队使用猕猴和绒猴带来的一些最新的成像进展。这些包括光遗传学的技术进展；电压、钙和谷氨酸敏感的染料成像；双光子和广域光学成像；病毒传递；指示物和光激活蛋白的遗传表达，从而使HAP中数以万计的已识别皮质神经元可视化。我们描述了NHP中电路和细胞成像工具的许多最新进展的子集，这里主要集中在2019年神经科学学会年会上相应的小型研讨会上提交的研究。
Novel genetically encoded tools and advanced microscopy methods have revolutionized neural circuit analyses in insects and rodents over the last two decades. Whereas numerous technical hurdles originally barred these methodologies from success in nonhuman primates (NHPs), current research has started to overcome those barriers. In some cases, methodological advances developed with NHPs have even surpassed their precursors. One such advance includes new ultra-large imaging windows on NHP cortex, which are larger than the entire rodent brain and allow analysis unprecedented ultra-large-scale circuits. NHP imaging chambers now remain patent for periods longer than a mouse's lifespan, allowing for long-term all-optical interrogation of identified circuits and neurons over time-frames that are relevant to human cognitive development. Here we present some recent imaging advances brought forth by research teams using macaques and marmosets. These include technical developments in optogenetics; voltage-, calcium- and glutamate-sensitive dye imaging; two-photon and wide-field optical imaging; viral delivery; and genetic expression of indicators and light-activated proteins that result in the visualization of tens of thousands of identified cortical neurons in NHPs. We describe a subset of the many recent advances in circuit and cellular imaging tools in NHPs focusing here primarily on the research presented during the corresponding mini-symposium at the 2019 Society for Neuroscience annual meeting.