論文 - 詳細
| RRC ID | 81870 |
|---|---|
| 著者 | Miyake T, Tanaka K, Inoue Y, Nagai Y, Nishimura R, Seta T, Nakagawa S, Inoue KI, Hasegawa E, Minamimoto T, Doi M. |
| タイトル | Size-reduced DREADD derivatives for AAV-assisted multimodal chemogenetic control of neuronal activity and behavior. |
| ジャーナル | Cell Rep Methods |
| 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 miniDq and miniDi, which inherit the basic receptor properties from the Gq-coupled excitatory receptor hM3Dq and the Gi-coupled inhibitory receptor hM4Di, 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 miniDq 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 miniDq, but not miniDi, 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. |
| 巻・号 | 4(10) |
| ページ | 100881 |
| 公開日 | 2024-10-21 |
| DOI | 10.1016/j.crmeth.2024.100881 |
| PII | S2667-2375(24)00264-9 |
| PMID | 39437713 |
| MeSH | Animals Behavior, Animal / drug effects Clozapine / analogs & derivatives Clozapine / pharmacology Dependovirus* / genetics Designer Drugs* / chemistry Designer Drugs* / pharmacology Genetic Vectors* HEK293 Cells Humans Macaca fascicularis* Male Mice Neurons* / drug effects Neurons* / metabolism Receptors, Opioid, kappa / genetics Receptors, Opioid, kappa / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 67 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pAAV-hSyn-miniDq-P2A-mCherry (RDB20117) pAAV-hSyn-miniDi-P2A-mCherry (RDB20118) pAAV-hSyn-miniDq-mCherry-P2A-HA-KORD (RDB20119) |