A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains

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.

書誌情報

The EMBO Journal

巻 40, 号 22, p. e107757, 発行日 2021-10

出版者

EMBO Press

ISSN

収録物識別子タイプ

ISSN

収録物識別子

0261-4189

PubMed番号

識別子タイプ

PMID

Versions

Ver.1

2023-05-15 17:08:48.093819

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