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Título

Reversible silencing of endogenous receptors in intact brain tissue using 2-photon pharmacology

AutorPittolo, Silvia; Lee, Hyojung; Lladó, Anna; Tosi, Sébastien; Bosch, Miquel; Bardia, Lídia; Gómez-Santacana, Xavier CSIC ORCID; Llebaria, Amadeu CSIC ORCID; Soriano, Eduardo; Colombelli, Julien; Poskanzer, Kira E.; Perea, Gertrudis CSIC ORCID; Gorostiza, Pau
Palabras clave2-photon pharmacology
Functional silencing
Pharmacological selectivity
Photoactivation
Photopharmacology
Fecha de publicación2-jul-2019
EditorNational Academy of Sciences (U.S.)
CitaciónProceedings of the National Academy of Sciences of the United States of America 116 (27): 13680-13689 (2019)
ResumenThe physiological activity of proteins is often studied with loss-of-function genetic approaches, but the corresponding phenotypes develop slowly and can be confounding. Photopharmacology allows direct, fast, and reversible control of endogenous protein activity, with spatiotemporal resolution set by the illumination method. Here, we combine a photoswitchable allosteric modulator (alloswitch) and 2-photon excitation using pulsed near-infrared lasers to reversibly silence metabotropic glutamate 5 (mGlu5) receptor activity in intact brain tissue. Endogenous receptors can be photoactivated in neurons and astrocytes with pharmacological selectivity and with an axial resolution between 5 and 10 μm. Thus, 2-photon pharmacology using alloswitch allows investigating mGlu5-dependent processes in wild-type animals, including synaptic formation and plasticity, and signaling pathways from intracellular organelles. © 2019 National Academy of Sciences. All rights reserved.
Versión del editorhttps://doi.org/10.1073/pnas.1900430116
URIhttp://hdl.handle.net/10261/200686
DOI10.1073/pnas.1900430116
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