期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12236-z
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资金
- NIDA [ZIA000069]
- NIMH [ZIAMH002793, ZIAMH002795]
- NIA [R21AG054802]
- NINDS
- NIBIB [P41EB024495]
- European Research Council (ERC) [679714 STC]
- Lundbeck Foundation [R264-2017-3189]
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002793, ZIAMH002795] Funding Source: NIH RePORTER
- European Research Council (ERC) [679714] Funding Source: European Research Council (ERC)
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated F-18 positron emission tomography (PET) DREADD radiotracer, [F-18]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [F-18]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping.
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