Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo
Purpose: To interrogate animal physiology in vivo, there is a lack of non-genetic methods to control the activity of endogenous proteins with pharmacological and spatiotemporal precision. To address this need, we recently developed targeted covalent photoswitchable (TCP) compounds that enable the re...
| Autores: | , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/223792 |
| Acceso en línea: | https://hdl.handle.net/2445/223792 http://hdl.handle.net/2445/223792 |
| Access Level: | acceso abierto |
| Palabra clave: | Calci Neurones Fotofarmacologia Hipocamp (Cervell) Calcium Neurons Photopharmacology Hippocampus (Brain) |
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Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivoGarrido Charles, AidaBosch Pita, MiquelLee, HyojungRovira, XavierPittolo, SilviaLlobet Berenguer, Artur, 1972-Wong, Hovy Ho-WaiTrapero, AnaMatera, CarloPapotto, ClaudioSerra, CarmeLlebaria Soldevila, AmadeuSoriano García, EduardoSánchez-Vives, María VictoriaHolt, Christine E.Gorostiza Langa, Pablo IgnacioCalciNeuronesFotofarmacologiaHipocamp (Cervell)CalciumNeuronsPhotopharmacologyHippocampus (Brain)Purpose: To interrogate animal physiology in vivo, there is a lack of non-genetic methods to control the activity of endogenous proteins with pharmacological and spatiotemporal precision. To address this need, we recently developed targeted covalent photoswitchable (TCP) compounds that enable the remote control of endogenous glutamate receptors (GluRs) using light. Methods: We combine the photopharmacological effector TCP9 with neuronal activity sensors to demonstrate all-optical reversible control of endogenous GluRs across multiple spatiotemporal scales in rat brain tissue ex vivo and in Xenopus tadpole brains in vivo. Findings: TCP9 allows photoactivation of neuronal ensembles, individual neurons, and single synapses in ex vivo tissue and in intact brain in vivo, which is challenging using optogenetics and neurotransmitter uncaging. TCP9 covalently targets AMPA and kainate receptors, maintaining their functionality and photoswitchability for extended periods (>8 h) after a single compound application. This allows tracking endogenous receptor physiology during synaptic plasticity events such as the reduction of functional AMPA receptors during long-term depression in hippocampal neurons. Conclusion: TCP9 is a unique non-invasive tool for durable labeling, reversible photoswitching, and functional tracking of native receptors in brain tissue without genetic manipulation.Elsevier2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/223792http://hdl.handle.net/2445/223792Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.brs.2025.09.005Brain Stimulation, 2025, vol. 18, num.6, p. 1779-1793https://doi.org/10.1016/j.brs.2025.09.005cc-by-nc (c) Garrido Charles, Aida et al., 2025http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2237922026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| title |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| spellingShingle |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo Garrido Charles, Aida Calci Neurones Fotofarmacologia Hipocamp (Cervell) Calcium Neurons Photopharmacology Hippocampus (Brain) |
| title_short |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| title_full |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| title_fullStr |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| title_full_unstemmed |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| title_sort |
Photoswitching endogenous glutamate receptors in neural ensembles and single synapses in vivo |
| dc.creator.none.fl_str_mv |
Garrido Charles, Aida Bosch Pita, Miquel Lee, Hyojung Rovira, Xavier Pittolo, Silvia Llobet Berenguer, Artur, 1972- Wong, Hovy Ho-Wai Trapero, Ana Matera, Carlo Papotto, Claudio Serra, Carme Llebaria Soldevila, Amadeu Soriano García, Eduardo Sánchez-Vives, María Victoria Holt, Christine E. Gorostiza Langa, Pablo Ignacio |
| author |
Garrido Charles, Aida |
| author_facet |
Garrido Charles, Aida Bosch Pita, Miquel Lee, Hyojung Rovira, Xavier Pittolo, Silvia Llobet Berenguer, Artur, 1972- Wong, Hovy Ho-Wai Trapero, Ana Matera, Carlo Papotto, Claudio Serra, Carme Llebaria Soldevila, Amadeu Soriano García, Eduardo Sánchez-Vives, María Victoria Holt, Christine E. Gorostiza Langa, Pablo Ignacio |
| author_role |
author |
| author2 |
Bosch Pita, Miquel Lee, Hyojung Rovira, Xavier Pittolo, Silvia Llobet Berenguer, Artur, 1972- Wong, Hovy Ho-Wai Trapero, Ana Matera, Carlo Papotto, Claudio Serra, Carme Llebaria Soldevila, Amadeu Soriano García, Eduardo Sánchez-Vives, María Victoria Holt, Christine E. Gorostiza Langa, Pablo Ignacio |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Calci Neurones Fotofarmacologia Hipocamp (Cervell) Calcium Neurons Photopharmacology Hippocampus (Brain) |
| topic |
Calci Neurones Fotofarmacologia Hipocamp (Cervell) Calcium Neurons Photopharmacology Hippocampus (Brain) |
| description |
Purpose: To interrogate animal physiology in vivo, there is a lack of non-genetic methods to control the activity of endogenous proteins with pharmacological and spatiotemporal precision. To address this need, we recently developed targeted covalent photoswitchable (TCP) compounds that enable the remote control of endogenous glutamate receptors (GluRs) using light. Methods: We combine the photopharmacological effector TCP9 with neuronal activity sensors to demonstrate all-optical reversible control of endogenous GluRs across multiple spatiotemporal scales in rat brain tissue ex vivo and in Xenopus tadpole brains in vivo. Findings: TCP9 allows photoactivation of neuronal ensembles, individual neurons, and single synapses in ex vivo tissue and in intact brain in vivo, which is challenging using optogenetics and neurotransmitter uncaging. TCP9 covalently targets AMPA and kainate receptors, maintaining their functionality and photoswitchability for extended periods (>8 h) after a single compound application. This allows tracking endogenous receptor physiology during synaptic plasticity events such as the reduction of functional AMPA receptors during long-term depression in hippocampal neurons. Conclusion: TCP9 is a unique non-invasive tool for durable labeling, reversible photoswitching, and functional tracking of native receptors in brain tissue without genetic manipulation. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/223792 http://hdl.handle.net/2445/223792 |
| url |
https://hdl.handle.net/2445/223792 http://hdl.handle.net/2445/223792 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1016/j.brs.2025.09.005 Brain Stimulation, 2025, vol. 18, num.6, p. 1779-1793 https://doi.org/10.1016/j.brs.2025.09.005 |
| dc.rights.none.fl_str_mv |
cc-by-nc (c) Garrido Charles, Aida et al., 2025 http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc (c) Garrido Charles, Aida et al., 2025 http://creativecommons.org/licenses/by-nc/3.0/es/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
15 p. application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Patologia i Terapèutica Experimental) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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15,811543 |