Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells

Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses i...

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Autores: Ramírez Franco, José Jorge, Bartolomé-Martín, David, Alonso, Beatris, Torres Molina, Magdalena Isabel, Sánchez-Prieto Borja, José
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/129943
Acceso en línea:https://hdl.handle.net/20.500.14352/129943
Access Level:acceso abierto
Palabra clave:612.8.015
Neurociencias (Biológicas)
2490.02 Neuroquímica
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spelling Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cellsRamírez Franco, José JorgeBartolomé-Martín, DavidAlonso, BeatrisTorres Molina, Magdalena IsabelSánchez-Prieto Borja, José612.8.015Neurociencias (Biológicas)2490.02 NeuroquímicaCannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1α protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals.PLOSUniversidad Complutense de Madrid20142014-01-0120142014-01-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/129943reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available BFU2010-16947 CONTROL BIDIRECCIONAL DE LA LIBERACION DE GLUTAMATO POR EL RECEPTOR METABOTROPICO MGLUR7Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available BFU2009-07092-E ORGANIZACION DEL "51ST INTERNATIONAL CONFERENCE ON THE BIOSCIENCE OF LIPIDS"Ministerio de Sanidad y Consumo Not available RD06%2F0026%2F0016 RED NEUROVASCULAR (RENEVAS)open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1299432026-06-02T12:44:21Z
dc.title.none.fl_str_mv Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
title Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
spellingShingle Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
Ramírez Franco, José Jorge
612.8.015
Neurociencias (Biológicas)
2490.02 Neuroquímica
title_short Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
title_full Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
title_fullStr Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
title_full_unstemmed Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
title_sort Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells
dc.creator.none.fl_str_mv Ramírez Franco, José Jorge
Bartolomé-Martín, David
Alonso, Beatris
Torres Molina, Magdalena Isabel
Sánchez-Prieto Borja, José
author Ramírez Franco, José Jorge
author_facet Ramírez Franco, José Jorge
Bartolomé-Martín, David
Alonso, Beatris
Torres Molina, Magdalena Isabel
Sánchez-Prieto Borja, José
author_role author
author2 Bartolomé-Martín, David
Alonso, Beatris
Torres Molina, Magdalena Isabel
Sánchez-Prieto Borja, José
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612.8.015
Neurociencias (Biológicas)
2490.02 Neuroquímica
topic 612.8.015
Neurociencias (Biológicas)
2490.02 Neuroquímica
description Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1α protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01
2014
2014-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/129943
url https://hdl.handle.net/20.500.14352/129943
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available BFU2010-16947 CONTROL BIDIRECCIONAL DE LA LIBERACION DE GLUTAMATO POR EL RECEPTOR METABOTROPICO MGLUR7
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available BFU2009-07092-E ORGANIZACION DEL "51ST INTERNATIONAL CONFERENCE ON THE BIOSCIENCE OF LIPIDS"
Ministerio de Sanidad y Consumo Not available RD06%2F0026%2F0016 RED NEUROVASCULAR (RENEVAS)
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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