TY - JOUR
T1 - A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains
AU - Shimojo, Masafumi
AU - Ono, Maiko
AU - Takuwa, Hiroyuki
AU - Mimura, Koki
AU - Nagai, Yuji
AU - Fujinaga, Masayuki
AU - Kikuchi, Tatsuya
AU - Okada, Maki
AU - Seki, Chie
AU - Tokunaga, Masaki
AU - Maeda, Jun
AU - Takado, Yuhei
AU - Takahashi, Manami
AU - Minamihisamatsu, Takeharu
AU - Zhang, Ming Rong
AU - Tomita, Yutaka
AU - Suzuki, Norihiro
AU - Maximov, Anton
AU - Suhara, Tetsuya
AU - Minamimoto, Takafumi
AU - Sahara, Naruhiko
AU - Higuchi, Makoto
N1 - Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2021/11/15
Y1 - 2021/11/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85117067505
UR - https://www.scopus.com/pages/publications/85117067505#tab=citedBy
U2 - 10.15252/embj.2021107757
DO - 10.15252/embj.2021107757
M3 - Article
C2 - 34636430
AN - SCOPUS:85117067505
SN - 0261-4189
VL - 40
JO - EMBO Journal
JF - EMBO Journal
IS - 22
M1 - e107757
ER -