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Translational PET applications for brain circuit mapping with transgenic neuromodulation tools
Pharmacology Biochemistry and Behavior ( IF 3.3 ) Pub Date : 2021-02-04 , DOI: 10.1016/j.pbb.2021.173147
Matthew A Boehm 1 , Jordi Bonaventura 2 , Juan L Gomez 2 , Oscar Solís 2 , Elliot A Stein 2 , Charles W Bradberry 2 , Michael Michaelides 3
Affiliation  

Transgenic neuromodulation tools have transformed the field of neuroscience over the past two decades by enabling targeted manipulation of neuronal populations and circuits with unprecedented specificity. Chemogenetic and optogenetic neuromodulation systems are among the most widely used and allow targeted control of neuronal activity through the administration of a selective compound or light, respectively. Innovative genetic targeting strategies are utilized to transduce specific cells to express transgenic receptors and opsins capable of manipulating neuronal activity. These allow mapping of neuroanatomical projection sites and link cellular manipulations with brain circuit functions and behavior. As these tools continue to expand knowledge of the nervous system in preclinical models, developing translational applications for human therapies is becoming increasingly possible. However, new strategies for implementing and monitoring transgenic tools are needed for safe and effective use in translational research and potential clinical applications. A major challenge for such applications is the need to track the location and function of chemogenetic receptors and opsins in vivo, and new developments in positron emission tomography (PET) imaging techniques offer promising solutions. The goal of this review is to summarize current research combining transgenic tools with PET for in vivo mapping and manipulation of brain circuits and to propose future directions for translational applications.



中文翻译:


使用转基因神经调节工具进行脑回路映射的转化 PET 应用



转基因神经调节工具在过去二十年中改变了神经科学领域,能够以前所未有的特异性对神经元群体和回路进行有针对性的操纵。化学遗传学和光遗传学神经调节系统是使用最广泛的系统之一,可以分别通过选择性化合物或光的施用来有针对性地控制神经元活动。利用创新的遗传靶向策略来转导特定细胞以表达能够操纵神经元活动的转基因受体和视蛋白。这些可以绘制神经解剖学投影部位的图谱,并将细胞操作与脑回路功能和行为联系起来。随着这些工具不断扩展临床前模型中神经系统的知识,开发人类疗法的转化应用变得越来越可能。然而,为了在转化研究和潜在的临床应用中安全有效地使用,需要实施和监测转基因工具的新策略。此类应用的一个主要挑战是需要跟踪体内化学遗传受体和视蛋白的位置和功能,而正电子发射断层扫描(PET)成像技术的新发展提供了有希望的解决方案。本综述的目的是总结当前将转基因工具与 PET 相结合用于大脑回路的体内绘图和操作的研究,并提出转化应用的未来方向。

更新日期:2021-03-11
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