Evidence map›Paper›PMID 31063250›Full record

ArticleThe European journal of neuroscience2019

Ultrastructural localization of DREADDs in monkeys.

Adriana Galvan, Jessica Raper, Xing Hu, Jean-François Paré, Jordi Bonaventura, Christopher T Richie, Michael Michaelides, Sascha A L Mueller, Patrick H Roseboom, Jonathan A Oler and 3 more

Abstract read
In one paragraph

Article in The European journal of neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Article
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  6. Combining Machine Learning and Multiplexed,bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Applications of chemogenetics in non-human primates.Current opinion in pharmacology · 2022
    Review
  18. Article
  19. Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  20. Characterization of DREADD receptor expression and function in rhesus macaques trained to discriminate ethanol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Adriana GalvanYerkes National Primate Research Center, Emory University, Atlanta, Georgia.ORCID 0000-0001-9939-0130
Jessica RaperYerkes National Primate Research Center, Emory University, Atlanta, Georgia.
Xing HuYerkes National Primate Research Center, Emory University, Atlanta, Georgia.
Jean-François ParéYerkes National Primate Research Center, Emory University, Atlanta, Georgia.
Jordi BonaventuraBiobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse (NIDA), Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
Christopher T RichieGenetic Engineering and Viral Vector Core, National Institute on Drug Abuse (NIDA), Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
Michael MichaelidesBiobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse (NIDA), Intramural Research Program, National Institutes of Health, Baltimore, Maryland.
Sascha A L MuellerDepartment of Psychiatry, University of Wisconsin, Madison, Wisconsin.
Patrick H RoseboomDepartment of Psychiatry, University of Wisconsin, Madison, Wisconsin.
Jonathan A OlerDepartment of Psychiatry, University of Wisconsin, Madison, Wisconsin.
Ned H KalinDepartment of Psychiatry, University of Wisconsin, Madison, Wisconsin.
Randy A HallDepartment of Pharmacology, Emory University School of Medicine, Atlanta, Georgia.
Yoland SmithYerkes National Primate Research Center, Emory University, Atlanta, Georgia.

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
Biobehavioral Imaging and Molecular Neuropsychopharmacology of Substance Abuse MechanismsZIADA000069 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI MICHAELIDES, MICHAEL · 2016 to 2025
$18.9M
DEVELOPMENT AND REGULATION OF EMOTION IN PRIMATESR01MH046729 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI Ned H Kalin · 1990 to 2026
$15.3M
Summer Research ExperienceP50MH100031 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI KALIN, NED H · 2013 to 2017
$10.4M
Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
NIGMS NIH HHS T32 GM008688NIH HHS P51 OD011106NIH HHS P51 OD011132NIMH NIH HHS R01 MH046729
6 · The paper itself

Abstract

Designer receptors exclusively activated by designer drugs (DREADDs) are extensively used to modulate neuronal activity in rodents, but their use in primates remains limited. An essential need that remains is the demonstration that DREADDs are efficiently expressed on the plasma membrane of primate neurons. To address this issue, electron microscopy immunogold was used to determine the subcellular localization of the AAV vector-induced DREADDs hM4Di and hM3Dq fused to different tags in various brain areas of rhesus monkeys and mice. When hM4Di was fused to mCherry, the immunogold labelling was mostly confined to the intracellular space, and poorly expressed at the plasma membrane in monkey dendrites. In contrast, the hM4Di-mCherry labelling was mostly localized to the dendritic plasma membrane in mouse neurons, suggesting species differences in the plasma membrane expression of these exogenous proteins. The lack of hM4Di plasma membrane expression may limit the functional effects of systemic administration of DREADD-actuators in monkey neurons. Removing the mCherry and fusing of hM4Di with the haemagglutinin (HA) tag resulted in strong neuronal plasma membrane immunogold labelling in both monkeys and mice neurons. Finally, hM3Dq-mCherry was expressed mostly at the plasma membrane in monkey neurons, indicating that the fusion of mCherry with hM3Dq does not hamper membrane incorporation of this specific DREADD. Our results suggest that the pattern of ultrastructural expression of DREADDs in monkey neurons depends on the DREADD/tag combination. Therefore, a preliminary characterization of plasma membrane expression of specific DREADD/tag combinations is recommended when using chemogenetic approaches in primates.

Indexed as

AnimalsBrainCell MembraneDendritesFemaleMacaca mulattaMaleMiceNeuronsReceptors, G-Protein-CoupledReceptors, G-Protein-CoupledHA-taghM3DqhM4DiimmunogoldmCherry

Identifiers

PMID31063250
PMCPMC6777996

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.