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.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.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.doi http://dx.doi.org/10.3390/ijms231710114
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/55492
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2022 Sep 4;23(17):10114
• 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 © 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• 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.title Reversible photocontrol of dopaminergic transmission in wild-type animals
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion