Size-reduced DREADD derivatives for AAV-assisted multimodal chemogenetic control of neuronal activity and behavior.

Autor: Miyake T; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan. Electronic address: tmiyake@pharm.kyoto-u.ac.jp., Tanaka K; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan., Inoue Y; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan., Nagai Y; Advanced Neuroimaging Center, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Nishimura R; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan., Seta T; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan., Nakagawa S; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan., Inoue KI; Systems Neuroscience Section, Center for the Evolutionary Origins of Human Behavior, Kyoto University, Inuyama 484-8506, Japan., Hasegawa E; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan., Minamimoto T; Advanced Neuroimaging Center, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Doi M; Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan. Electronic address: doimasao@pharm.kyoto-u.ac.jp.
Jazyk: angličtina
Zdroj: Cell reports methods [Cell Rep Methods] 2024 Oct 21; Vol. 4 (10), pp. 100881.
DOI: 10.1016/j.crmeth.2024.100881
Abstrakt: 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 q and miniD i , which inherit the basic receptor properties from the G q -coupled excitatory receptor hM3D q and the G i -coupled inhibitory receptor hM4D i , 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 q 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 q , but not miniD i , 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.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: