Designer receptors exclusively activated by designer drugs (DREADDs) are widely used in rodents to manipulate neuronal activity and establish causal links between structure and function. Their utilization in non‐human primates (NHPs) is, however, limited and their efficacy still debated. Here, we recorded and examined the neuronal activity in the hM4Di DREADD‐transduced and hM4Di DREADD‐free GPe of two anesthetized animals following local intra‐GPe microinjection of clozapine‐N‐oxide (CNO). Our results revealed that the neuronal activity of the well‐isolated units recorded in the hM4Di DREADD‐transduced GPe exhibited diverse patterns in timing and polarity (increase/decrease) of firing rate modulations following CNO injection. Nevertheless, significant decreases in activity were more frequent (and more pronounced) than significant increases in activity during CNO injection (6/18 vs. 3/18 units) and were exclusive after CNO Injection (8/18 units). In contrast, only one of the 8 well‐isolated units recorded in hM4Di DREADD‐free GPe exhibited a significant increase in activity after CNO injection. Overall, the number of units exhibiting a significant period‐related decrease following CNO injection was significantly larger in hM4Di DREADD‐transduced GPe than in the hM4Di DREADD‐free GPe (8/18 [44.4%] vs. 0/8 [0%]). Moreover, postmortem histochemical analysis revealed that hM4Di DREADDs were expressed at high level in the GPe neurons located in the vicinity of the viral vector injection sites. Our results therefore show in vivo hM4Di DREADD‐based inhibition of pallidal neurons in the NHP model and reinforce the view that DREADD technology can be effective in NHPs.

中文翻译：

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在非人类灵长类动物中基于DREADD的苍白神经元调节的体内电生理学验证

被设计药物（DREADDs）专门激活的设计受体广泛用于啮齿动物中，以操纵神经元活动并在结构与功能之间建立因果关系。然而，它们在非人类灵长类动物（NHPs）中的应用受到限制，其功效仍存在争议。在这里，我们记录并检查了在局部GPe内显微注射氯氮平-N-氧化物（CNO）后两只麻醉动物的hM4Di DREADD转导和hM4Di DREADD无GPe中的神经元活性。我们的研究结果表明，在hM4Di DREADD转导的GPe中记录的完全隔离的单元的神经元活动在CNO注射后的发射速率调节的时机和极性（增加/减少）中表现出多种模式。尽管如此，与CNO注射期间活动显着增加（6/18与3/18单位）相比，活动显着减少的发生频率更频繁（且更明显），并且在CNO注射后活动的显着增加除外（8/18单位）。相比之下，在无hM4Di DREADD的GPe中记录的8个完全隔离的单位中，只有1个在CNO注射后表现出明显的活性增加。总体而言，hM4Di DREADD转导的GPe中CNO注射后表现出明显的与时期相关的减少的单位数量明显大于无hM4Di DREADD的GPe中的单位数量（8/18 [44.4％]比0/8 [0％] ）。此外，死后组织化学分析显示，hM4Di DREADDs在病毒载体注射位点附近的GPe神经元中高水平表达。