In vivo electrophysiological validation of DREADD‐based modulation of pallidal neurons in the non‐human primate. (11th May 2020)

• Record Type: Journal Article
• Authors: Deffains, Marc; Nguyen, Tho Haï; Orignac, Hugues; Biendon, Nathalie; Dovero, Sandra; Bezard, Erwan; Boraud, Thomas
• Is Part Of: European journal of neuroscience. Volume 53:Number 7(2021)
• Page Start: 2192
• Page End: 2204
• Publication Date: 2020-05-11
• Subjects: chemogenetics -- external globus pallidus -- monkey -- neuronal recordings; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.14746
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: 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. Abstract : Although DREADD technology is widely used in rodents, its efficacy in non‐human primates (NHPs) is still debated. Local CNO microinjections produce robust DREADD‐based decreases in activity in the hM4Di DREADD‐transduced NHP external globus pallidus (GPe). This study is the first to demonstrate in vivo DREADD‐based modulation of the neuronal activity in the NHP.