A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains.
Animals
Brain
/ cytology
Callithrix
Carbon Radioisotopes
/ chemistry
Fluorine Radioisotopes
/ chemistry
Genes, Reporter
HEK293 Cells
Humans
Male
Mice, Inbred C57BL
Molecular Imaging
/ methods
Nerve Net
/ diagnostic imaging
Positron-Emission Tomography
/ methods
Proteins
/ analysis
Radiopharmaceuticals
/ chemical synthesis
Tetrahydrofolate Dehydrogenase
/ genetics
Trimethoprim
/ analogs & derivatives
PET
fluorescence
neural circuit
non-invasive
reporter imaging
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 11 2021
15 11 2021
Historique:
revised:
24
08
2021
received:
17
01
2021
accepted:
31
08
2021
pubmed:
13
10
2021
medline:
4
1
2022
entrez:
12
10
2021
Statut:
ppublish
Résumé
Positron emission tomography (PET) allows biomolecular tracking but PET monitoring of brain networks has been hampered by a lack of suitable reporters. Here, we take advantage of bacterial dihydrofolate reductase, ecDHFR, and its unique antagonist, TMP, to facilitate in vivo imaging in the brain. Peripheral administration of radiofluorinated and fluorescent TMP analogs enabled PET and intravital microscopy, respectively, of neuronal ecDHFR expression in mice. This technique can be used to the visualize neuronal circuit activity elicited by chemogenetic manipulation in the mouse hippocampus. Notably, ecDHFR-PET allows mapping of neuronal projections in non-human primate brains, demonstrating the applicability of ecDHFR-based tracking technologies for network monitoring. Finally, we demonstrate the utility of TMP analogs for PET studies of turnover and self-assembly of proteins tagged with ecDHFR mutants. These results establish opportunities for a broad spectrum of previously unattainable PET analyses of mammalian brain circuits at the molecular level.
Identifiants
pubmed: 34636430
doi: 10.15252/embj.2021107757
pmc: PMC8591537
doi:
Substances chimiques
Carbon Radioisotopes
0
Carbon-11
0
Fluorine Radioisotopes
0
Proteins
0
Radiopharmaceuticals
0
Trimethoprim
AN164J8Y0X
Tetrahydrofolate Dehydrogenase
EC 1.5.1.3
Fluorine-18
GZ5I74KB8G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e107757Subventions
Organisme : NINDS NIH HHS
ID : R01 NS087026
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1 MH123224
Pays : United States
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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