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灵长类动物皮层网络中的光遗传学

Optogenetics in primate cortical networks.

作者信息

Merlin Sam, Vidyasagar Trichur

机构信息

Medical Science, School of Science, Western Sydney University, Campbelltown, NSW, Australia.

Department of Optometry and Vision Sciences, School of Health Science, The University of Melbourne, Parkville, VIC, Australia.

出版信息

Front Neuroanat. 2023 May 22;17:1193949. doi: 10.3389/fnana.2023.1193949. eCollection 2023.

Abstract

The implementation of optogenetics in studies on non-human primates has generally proven quite difficult, but recent successes have paved the way for its rapid increase. Limitations in the genetic tractability in primates, have been somewhat overcome by implementing tailored vectors and promoters to maximize expression and specificity in primates. More recently, implantable devices, including microLED arrays, have made it possible to deliver light deeper into brain tissue, allowing targeting of deeper structures. However, the greatest limitation in applying optogenetics to the primate brain is the complex connections that exist within many neural circuits. In the past, relatively cruder methods such as cooling or pharmacological blockade have been used to examine neural circuit functions, though their limitations were well recognized. In some ways, similar shortcomings remain for optogenetics, with the ability to target a single component of complex neural circuits being the greatest challenge in applying optogenetics to systems neuroscience in primate brains. Despite this, some recent approaches combining Cre-expressing and Cre-dependent vectors have overcome some of these limitations. Here we suggest that optogenetics provides its greatest advantage to systems neuroscientists when applied as a specific tool to complement the techniques of the past, rather than necessarily replacing them.

摘要

在非人类灵长类动物研究中实施光遗传学通常已证明相当困难,但最近的成功为其迅速发展铺平了道路。通过实施定制载体和启动子以最大化灵长类动物中的表达和特异性,灵长类动物遗传易处理性方面的局限性已在一定程度上得到克服。最近,包括微型发光二极管阵列在内的可植入设备已使将光更深地传递到脑组织中成为可能,从而能够靶向更深层的结构。然而,将光遗传学应用于灵长类动物大脑的最大限制是许多神经回路中存在的复杂连接。过去,人们使用相对粗糙的方法,如冷却或药物阻断来检查神经回路功能,尽管其局限性已得到充分认识。在某些方面,光遗传学也存在类似的缺点,能够靶向复杂神经回路的单个组件是将光遗传学应用于灵长类动物大脑系统神经科学的最大挑战。尽管如此,最近一些将表达Cre和依赖Cre的载体相结合的方法已经克服了其中一些局限性。在此我们建议,当光遗传学作为一种特定工具来补充过去的技术而不一定取代它们时,它为系统神经科学家提供了最大的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c96/10239886/e8c12fdc2d04/fnana-17-1193949-g001.jpg

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