Three-Photon Infrared Stimulation of Endogenous Neuroreceptors in Vivo.
Por:
Sortino R, Cunquero M, Castro-Olvera G, Gelabert R, Moreno M, Riefolo F, Matera C, Fernandez-Castillo N, Agnetta L, Decker M, Lluch JM, Hernando J, Loza-Alvarez P and Gorostiza P
Publicada:
18 dic 2023
Ahead of Print:
20 nov 2023
Resumen:
To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton excitation, and has promoted two-photon photopharmacology and optogenetics. However, three-photon brain stimulation in vivo remains to be demonstrated. We report the regulation of neuronal activity in zebrafish larvae by three-photon excitation of a photoswitchable muscarinic agonist at 50 pM, a billion-fold lower concentration than used for uncaging, and with mid-infrared light of 1560 nm, the longest reported photoswitch wavelength. Robust, physiologically relevant photoresponses allow modulating brain activity in wild-type animals with spatiotemporal and pharmacological precision. Computational calculations predict that azobenzene-based ligands have high three-photon absorption cross-section and can be used directly with pulsed infrared light. The expansion of three-photon pharmacology will deeply impact basic neurobiology and neuromodulation phototherapies.
Filiaciones:
Sortino R:
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, 08028, Barcelona, Spain
CIBER-BBN, ISCIII, 28029, Madrid, Spain
Cunquero M:
ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860, Castelldefels (Barcelona), Spain
Castro-Olvera G:
ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860, Castelldefels (Barcelona), Spain
Gelabert R:
Departament de Química, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain
Moreno M:
Departament de Química, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain
Riefolo F:
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, 08028, Barcelona, Spain
CIBER-BBN, ISCIII, 28029, Madrid, Spain
Current address: Teamit Institute, Partnerships, Barcelona Health Hub, 08025, Barcelona, Spain
Matera C:
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, 08028, Barcelona, Spain
CIBER-BBN, ISCIII, 28029, Madrid, Spain
Current address: Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
Fernandez-Castillo N:
CIBER-BBN, ISCIII, 28029, Madrid, Spain
Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain
Institut de Biomedicina de la, Universitat de Barcelona (IBUB), 08028, Barcelona, Spain
Institut de Recerca Sant Joan de Déu (IRSJD), 08950, Esplugues de Llobregat, Spain
Agnetta L:
Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Ludwig Maximilian University of Würzburg, 97074, Würzburg, Germany
Decker M:
Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Ludwig Maximilian University of Würzburg, 97074, Würzburg, Germany
Lluch JM:
Departament de Química, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain
Institut de Biotecnologia i de Biomedicina (IBB), UAB, 08193, Bellaterra, Spain
Hernando J:
Departament de Química, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain
Loza-Alvarez P:
ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860, Castelldefels (Barcelona), Spain
Gorostiza P:
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, 08028, Barcelona, Spain
CIBER-BBN, ISCIII, 28029, Madrid, Spain
Catalan Institution of Research and Advanced Studies (ICREA), 08010, Barcelona, Spain
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