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Reversible photocontrol of dopaminergic transmission in wild-type animals

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dc.contributor.author Matera, Carlo
dc.contributor.author Calvé Pérez, Pablo, 1993-
dc.contributor.author Casadó-Anguera, Verònica
dc.contributor.author Sortino, Rosalba
dc.contributor.author Gomila, Alexandre M.J.
dc.contributor.author Moreno, Estefanía
dc.contributor.author Gener, Thomas
dc.contributor.author Delgado-Sallent, Cristina
dc.contributor.author Nebot Forcada, Pau
dc.contributor.author Costazza, Davide
dc.contributor.author Conde-Berriozabal, Sara
dc.contributor.author Masana, Mercè
dc.contributor.author Hernando, Jordi
dc.contributor.author Casadó, Vicent
dc.contributor.author Puig Velasco, María Victoria
dc.contributor.author Gorostiza, Pau
dc.date.accessioned 2023-01-31T07:14:49Z
dc.date.available 2023-01-31T07:14:49Z
dc.date.issued 2022
dc.identifier.citation Matera C, Calvé P, Casadó-Anguera V, Sortino R, Gomila AMJ, Moreno E, Gener T, Delgado-Sallent C, Nebot P, Costazza D, Conde-Berriozabal S, Masana M, Hernando J, Casadó V, Puig MV, Gorostiza P. Reversible photocontrol of dopaminergic transmission in wild-type animals. Int J Mol Sci. 2022 Sep 4;23(17):10114. DOI: 10.3390/ijms231710114
dc.identifier.issn 1422-0067
dc.identifier.uri http://hdl.handle.net/10230/55492
dc.description.abstract Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.
dc.description.sponsorship This research was funded by EU Horizon 2020 Framework Programme for Research and Innovation: Human Brain Project WaveScalES, Specific Grant Agreement 2 No. 785907 and Specific Grant Agreement 3 No. 945539; NEUROPA project, Grant Agreement No. 863214; DEEPER project ICT-36-2020-101016787; European Union Regional Development Fund within the framework of the ERDF Operational Program of Catalonia 2014-2020: CECH project; Ministry of Science and Innovation DEEP RED grant PID2019-111493RB-I00 funded by MCIN/AEI/10.13039/501100011033; Ministerio de Economía y Competitividad and European Regional Development Funds: Grant no. SAF2017-87629-R to V.C., SAF2016-80726-R to M.V.P., SAF2017-88076-R to M.M.; AGAUR/Generalitat de Catalunya: CERCA Programme; Generalitat de Catalunya: Grant no. 2017-SGR-1442 to P.G., 2017-SGR-1497 to V.C., 2017-SGR-210 to M.V.P., and 2017-SGR-00465 to J.H.; Fundaluce and “la Caixa” foundations: ID 100010434, grant agreement LCF/PR/HR19/52160010.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Int J Mol Sci. 2022 Sep 4;23(17):10114
dc.rights © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.title Reversible photocontrol of dopaminergic transmission in wild-type animals
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/ijms231710114
dc.subject.keyword GPCR
dc.subject.keyword Azobenzene
dc.subject.keyword Behavior
dc.subject.keyword Brainwave
dc.subject.keyword Dopamine
dc.subject.keyword In vivo electrophysiology
dc.subject.keyword Optogenetics
dc.subject.keyword Optopharmacology
dc.subject.keyword Photochromism
dc.subject.keyword Photopharmacology
dc.subject.keyword Photoswitch
dc.subject.keyword Zebrafish
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/785907
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/945539
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/863214
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-111493RB-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-87629-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80726-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-88076-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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