Fast Photoswitchable Molecular Prosthetics Control Neuronal Activity in the Cochlea
| Autor: | Garrido-Charles, Aida, Huet, Antoine, Matera, Carlo, Thirumalai, Anupriya, Hernando, Jordi, Llebaria, Amadeu, Moser, Tobias, Gorostiza, Pau |
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| Přispěvatelé: | European Commission |
| Rok vydání: | 2022 |
| Předmět: |
Neurons
Neuronal activities Neural functions Photocontrol Glutamate receptor Prostheses and Implants General Chemistry Ligands Artificial control Neuronal control Neural circuits Biochemistry Electrical stimulations Catalysis Cochlea Optogenetics Colloid and Surface Chemistry Artificial control of neuronal activity Photo-switchable Prosthetic controls Ensure healthy lives and promote well-being for all at all ages |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Artificial control of neuronal activity enables the study of neural circuits and restoration of neural functions. Direct, rapid, and sustained photocontrol of intact neurons could overcome the limitations of established electrical stimulation such as poor selectivity. We have developed fast photoswitchable ligands of glutamate receptors (GluRs) to enable neuronal control in the auditory system. The new photoswitchable ligands induced photocurrents in untransfected neurons upon covalently tethering to endogenous GluRs and activating them reversibly with visible light pulses of a few milliseconds. As a proof of concept of these molecular prostheses, we applied them to the ultrafast synapses of auditory neurons of the cochlea that encode sound and provide auditory input to the brain. This drug-based method afforded the optical stimulation of auditory neurons of adult gerbils at hundreds of hertz without genetic manipulation that would be required for their optogenetic control. This indicates that the new photoswitchable ligands are also applicable to the spatiotemporal control of fast spiking interneurons in the brain. This research received funding from the European Union Research and Innovation Programme Horizon 2020─Human Brain Project SG3 (945539), DEEPER (ICT-36-2020–101016787), Agency for Management of University and Research Grants/Generalitat de Catalunya (CERCA Programme; 2017-SGR-1442 and 2017-SGR-1604 projects), Fonds Européen de Développement Économique et Régional (FEDER) funds, Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación and ERDF-FEDER European Fund (projects CTQ2017-89222-R and PID2020-120499RB-I00), and Fundaluce and “la Caixa” foundations (ID 100010434, agreement LCF/PR/HR19/52160010). The project Clúster Emergent del Cervell Humà (CECH, 001-P-001682) is cofinanced by the European Union Regional Development Fund within the framework of the ERDF Operational Program of Catalonia 2014–2020 with a grant of 50% of total eligible cost. A.G.-C. was supported by the fellowship BES-2014-068169 and Alexander von Humboldt Foundation. J.H. was supported by Agencia Estatal de Investigación (PID2019-106171RB-100/AEI/10.13039/501100011033) and Generalitat de Catalunya (2017 SGR00465). We thank chemical facility PCB staff (Unai Elezcano, Sònia Varon) and IBEC infrastructure staff (Isabel Oliveira, David Izquierdo). We thank Christiane Senger-Freitag, Sandra Gerke, and Sina Langer for technical support, Gerhard Hoch for his expert technical support, and Patricia Räke-Kügler for excellent administrative support. We thank Thomas Mager for providing the patch clamp setup. This work was funded by the European Research Council through the Advanced Grant “OptoHear” to T.M. under the European Union’s Horizon 2020 Research and Innovation program (grant agreement no. 670759), the Fraunhofer and Max-Planck Cooperation Program (NeurOpto grant) to T.M., was further supported by the German Research Foundation through the Priority Program 1926 “Next generation optogenetics” to A.H. and T.M., and the Leibniz Program (to T.M.) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy─EXC 2067/1-390729940 to A.H. and T.M. In addition, this research was supported by the Fakultätinternes Forschungförderungsprogramm from the Universitätsmedizin Göttingen, Georg-August-Universität Göttingen to A.H., and Fondation Pour l’Audition (FPA RD-2020-10) to T.M. Molecular graphics and analyses were performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311. We thank Dr. Vladimir Belov, Jurgen Bienert, and Jan Seikowski for HPLC and LC–MS measurements of final TCPfast products. |
| Databáze: | OpenAIRE |
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