In vivo electrophysiological validation of DREADD-based modulation of pallidal neurons in the non-human primate.
chemogenetics
external globus pallidus
monkey
neuronal recordings
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
06
04
2020
received:
03
01
2020
accepted:
07
04
2020
pubmed:
20
4
2020
medline:
30
6
2021
entrez:
20
4
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Clozapine
J60AR2IKIC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2192-2204Informations de copyright
© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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