[Epub ahead of print]

In vivo electrophysiological validation of DREADD-based modulation of pallidal neurons in the non-human primate.

Marc Deffains, Tho Haï Nguyen, Hugues Orignac, Nathalie Biendon, Sandra Dovero, Erwan Bezard, Thomas Boraud
Eur J Neurosci. 2020-05-11; :
DOI: 10.1111/ejn.14746

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In vivo electrophysiological validation of DREADD-based modulation of pallidal
neurons in the non-human primate.

Deffains M(1)(2), Nguyen TH(1)(2), Orignac H(1)(2), Biendon N(1)(2), Dovero
S(1)(2), Bezard E(1)(2), Boraud T(1)(2)(3).

Author information:
(1)Institut des Maladies Neurodégénératives (IMN), UMR 5293, Université de
Bordeaux, Bordeaux, France.
(2)Centre National de la Recherche Scientifique, IMN, UMR 5293, Bordeaux, France.
(3)IMN Clinique, Hôpital Pellegrin, Centre hospitalier Universitaire de Bordeaux,
Place Amélie Raba Léon, Bordeaux, France.

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.

© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

DOI: 10.1111/ejn.14746
PMID: 32306446

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