Translational PET applications for brain circuit mapping with transgenic neuromodulation tools.
Translational PET applications for brain circuit mapping with transgenic neuromodulation tools.
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翻译PET应用于转基因神经调节工具的脑电路制图。
DOI：
10.1016/j.pbb.2021.173147
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Michaelides M
中科院分区：
文献类型：
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作者：
Boehm MA;Bonaventura J;Gomez JL;Solís O;Stein EA;Bradberry CW;Michaelides M
在过去的二十年里，转基因神经调节工具以前所未有的特异性实现了对神经元群体和电路的定向操作，从而改变了神经科学领域。化学发生和光发生神经调节系统是应用最广泛的系统之一，它们分别通过给予选择性化合物或光来实现对神经元活动的靶向控制。创新的基因打靶策略被用来转导特定的细胞来表达能够操纵神经元活动的转基因受体和视蛋白。这些技术可以绘制神经解剖投影位置图，并将细胞操作与大脑回路功能和行为联系起来。随着这些工具在临床前模型中不断扩展神经系统的知识，为人类疗法开发翻译应用程序正变得越来越有可能。然而，为了在转化研究和潜在的临床应用中安全和有效地使用转基因工具，需要实施和监测转基因工具的新策略。这类应用的一个主要挑战是需要跟踪体内化学发生受体和视蛋白的位置和功能，正电子发射断层成像(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目前将转基因工具与正电子发射计算机断层成像(PET)相结合用于活体脑回路定位和操作的研究，并提出未来翻译应用的方向。
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.