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Size-reduced DREADD derivatives for AAV-assisted multimodal chemogenetic control of neuronal activity and behavior.
- Source :
-
Cell reports methods [Cell Rep Methods] 2024 Oct 21; Vol. 4 (10), pp. 100881. - Publication Year :
- 2024
-
Abstract
- Designer receptors exclusively activated by designer drugs (DREADDs) are engineered G-protein-coupled receptors that afford reversible manipulation of neuronal activity in vivo. Here, we introduce size-reduced DREADD derivatives miniD <subscript>q</subscript> and miniD <subscript>i</subscript> , which inherit the basic receptor properties from the G <subscript>q</subscript> -coupled excitatory receptor hM3D <subscript>q</subscript> and the G <subscript>i</subscript> -coupled inhibitory receptor hM4D <subscript>i</subscript> , respectively, while being approximately 30% smaller in size. Taking advantage of the compact size of the receptors, we generated an adeno-associated virus (AAV) vector carrying both miniD <subscript>q</subscript> and the other DREADD family receptor (κ-opioid receptor-based inhibitory DREADD [KORD]) within the maximum AAV capacity (4.7 kb), allowing us to modulate neuronal activity and animal behavior in both excitatory and inhibitory directions using a single viral vector. We confirmed that expressing miniD <subscript>q</subscript> , but not miniD <subscript>i</subscript> , allowed activation of striatum activity in the cynomolgus monkey (Macaca fascicularis). The compact DREADDs may thus widen the opportunity for multiplexed interrogation and/or intervention in neuronal regulation in mice and non-human primates.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Humans
Behavior, Animal drug effects
Mice
Receptors, Opioid, kappa metabolism
Receptors, Opioid, kappa genetics
Male
HEK293 Cells
Clozapine analogs & derivatives
Clozapine pharmacology
Dependovirus genetics
Neurons drug effects
Neurons metabolism
Genetic Vectors
Macaca fascicularis
Designer Drugs pharmacology
Designer Drugs chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2667-2375
- Volume :
- 4
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports methods
- Publication Type :
- Academic Journal
- Accession number :
- 39437713
- Full Text :
- https://doi.org/10.1016/j.crmeth.2024.100881