Presynaptic nanoscale components of retrograde synaptic signaling

Autores
Barti, Benjámin; Dudok, Barna; Kenesei, Kata; Zöldi, Miklós; Miczán, Vivien; Balla, Gyula Y.; Zala, Diana; Tasso, Mariana Patricia; Sagheddu, Claudia; Kisfali, Máté; Tóth, Blanka; Ledri, Marco; Vizi, E. Sylvester; Melis, Miriam; Barna, László; Lenkei, Zsolt; Soltész, Iván; Katona, István
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB1Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ9-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell–dependent manner.
Fil: Barti, Benjámin. Indiana University; Estados Unidos. Semmelweis University; Hungría. HUN-REN Institute of Experimental Medicine; Hungría
Fil: Dudok, Barna. HUN-REN Institute of Experimental Medicine; Hungría. Baylor College of Medicine; Estados Unidos. University of Stanford; Estados Unidos
Fil: Kenesei, Kata. HUN-REN Institute of Experimental Medicine; Hungría
Fil: Zöldi, Miklós. Indiana University; Estados Unidos. HUN-REN Institute of Experimental Medicine; Hungría. Semmelweis University; Hungría
Fil: Miczán, Vivien. HUN-REN Institute of Experimental Medicine; Hungría. HUN-REN Biological Research Center; Hungría
Fil: Balla, Gyula Y.. HUN-REN Institute of Experimental Medicine; Hungría. Semmelweis University; Hungría
Fil: Zala, Diana. Inserm; Francia
Fil: Tasso, Mariana Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Fil: Sagheddu, Claudia. Università Degli Studi Di Cagliari.; Italia
Fil: Kisfali, Máté. HUN-REN Institute of Experimental Medicine; Hungría. BiTrial Ltd.; Hungría
Fil: Tóth, Blanka. Budapest University of Technology and Economics; Hungría. Semmelweis University; Hungría
Fil: Ledri, Marco. HUN-REN Institute of Experimental Medicine; Hungría. Lund University; Suecia
Fil: Vizi, E. Sylvester. HUN-REN Institute of Experimental Medicine; Hungría
Fil: Melis, Miriam. Università Degli Studi Di Cagliari.; Italia
Fil: Barna, László. Indiana University; Estados Unidos
Fil: Lenkei, Zsolt. Inserm; Francia
Fil: Soltész, Iván. University of Stanford; Estados Unidos
Fil: Katona, István. Indiana University; Estados Unidos. HUN-REN Institute of Experimental Medicine; Hungría
Materia
CB1 receptor
Presynaptic component
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/240036
Acceder
id CONICETDig_9a05013de38257f885f4e0528a1ed30a
oai_identifier_str oai:ri.conicet.gov.ar:11336/240036
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Presynaptic nanoscale components of retrograde synaptic signalingBarti, BenjáminDudok, BarnaKenesei, KataZöldi, MiklósMiczán, VivienBalla, Gyula Y.Zala, DianaTasso, Mariana PatriciaSagheddu, ClaudiaKisfali, MátéTóth, BlankaLedri, MarcoVizi, E. SylvesterMelis, MiriamBarna, LászlóLenkei, ZsoltSoltész, IvánKatona, IstvánCB1 receptorPresynaptic componenthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB1Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ9-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell–dependent manner.Fil: Barti, Benjámin. Indiana University; Estados Unidos. Semmelweis University; Hungría. HUN-REN Institute of Experimental Medicine; HungríaFil: Dudok, Barna. HUN-REN Institute of Experimental Medicine; Hungría. Baylor College of Medicine; Estados Unidos. University of Stanford; Estados UnidosFil: Kenesei, Kata. HUN-REN Institute of Experimental Medicine; HungríaFil: Zöldi, Miklós. Indiana University; Estados Unidos. HUN-REN Institute of Experimental Medicine; Hungría. Semmelweis University; HungríaFil: Miczán, Vivien. HUN-REN Institute of Experimental Medicine; Hungría. HUN-REN Biological Research Center; HungríaFil: Balla, Gyula Y.. HUN-REN Institute of Experimental Medicine; Hungría. Semmelweis University; HungríaFil: Zala, Diana. Inserm; FranciaFil: Tasso, Mariana Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Sagheddu, Claudia. Università Degli Studi Di Cagliari.; ItaliaFil: Kisfali, Máté. HUN-REN Institute of Experimental Medicine; Hungría. BiTrial Ltd.; HungríaFil: Tóth, Blanka. Budapest University of Technology and Economics; Hungría. Semmelweis University; HungríaFil: Ledri, Marco. HUN-REN Institute of Experimental Medicine; Hungría. Lund University; SueciaFil: Vizi, E. Sylvester. HUN-REN Institute of Experimental Medicine; HungríaFil: Melis, Miriam. Università Degli Studi Di Cagliari.; ItaliaFil: Barna, László. Indiana University; Estados UnidosFil: Lenkei, Zsolt. Inserm; FranciaFil: Soltész, Iván. University of Stanford; Estados UnidosFil: Katona, István. Indiana University; Estados Unidos. HUN-REN Institute of Experimental Medicine; HungríaScience Advances is the American Association for the Advancement of Science2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/240036Barti, Benjámin; Dudok, Barna; Kenesei, Kata; Zöldi, Miklós; Miczán, Vivien; et al.; Presynaptic nanoscale components of retrograde synaptic signaling; Science Advances is the American Association for the Advancement of Science; Science Advances; 10; 22; 5-2024; 1-202375-2548CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.ado0077info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ado0077info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:52Zoai:ri.conicet.gov.ar:11336/240036instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:49:53.411CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Presynaptic nanoscale components of retrograde synaptic signaling
title Presynaptic nanoscale components of retrograde synaptic signaling
spellingShingle Presynaptic nanoscale components of retrograde synaptic signaling
Barti, Benjámin
CB1 receptor
Presynaptic component
title_short Presynaptic nanoscale components of retrograde synaptic signaling
title_full Presynaptic nanoscale components of retrograde synaptic signaling
title_fullStr Presynaptic nanoscale components of retrograde synaptic signaling
title_full_unstemmed Presynaptic nanoscale components of retrograde synaptic signaling
title_sort Presynaptic nanoscale components of retrograde synaptic signaling
dc.creator.none.fl_str_mv Barti, Benjámin
Dudok, Barna
Kenesei, Kata
Zöldi, Miklós
Miczán, Vivien
Balla, Gyula Y.
Zala, Diana
Tasso, Mariana Patricia
Sagheddu, Claudia
Kisfali, Máté
Tóth, Blanka
Ledri, Marco
Vizi, E. Sylvester
Melis, Miriam
Barna, László
Lenkei, Zsolt
Soltész, Iván
Katona, István
author Barti, Benjámin
author_facet Barti, Benjámin
Dudok, Barna
Kenesei, Kata
Zöldi, Miklós
Miczán, Vivien
Balla, Gyula Y.
Zala, Diana
Tasso, Mariana Patricia
Sagheddu, Claudia
Kisfali, Máté
Tóth, Blanka
Ledri, Marco
Vizi, E. Sylvester
Melis, Miriam
Barna, László
Lenkei, Zsolt
Soltész, Iván
Katona, István
author_role author
author2 Dudok, Barna
Kenesei, Kata
Zöldi, Miklós
Miczán, Vivien
Balla, Gyula Y.
Zala, Diana
Tasso, Mariana Patricia
Sagheddu, Claudia
Kisfali, Máté
Tóth, Blanka
Ledri, Marco
Vizi, E. Sylvester
Melis, Miriam
Barna, László
Lenkei, Zsolt
Soltész, Iván
Katona, István
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CB1 receptor
Presynaptic component
topic CB1 receptor
Presynaptic component
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB1Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ9-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell–dependent manner.
Fil: Barti, Benjámin. Indiana University; Estados Unidos. Semmelweis University; Hungría. HUN-REN Institute of Experimental Medicine; Hungría
Fil: Dudok, Barna. HUN-REN Institute of Experimental Medicine; Hungría. Baylor College of Medicine; Estados Unidos. University of Stanford; Estados Unidos
Fil: Kenesei, Kata. HUN-REN Institute of Experimental Medicine; Hungría
Fil: Zöldi, Miklós. Indiana University; Estados Unidos. HUN-REN Institute of Experimental Medicine; Hungría. Semmelweis University; Hungría
Fil: Miczán, Vivien. HUN-REN Institute of Experimental Medicine; Hungría. HUN-REN Biological Research Center; Hungría
Fil: Balla, Gyula Y.. HUN-REN Institute of Experimental Medicine; Hungría. Semmelweis University; Hungría
Fil: Zala, Diana. Inserm; Francia
Fil: Tasso, Mariana Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Fil: Sagheddu, Claudia. Università Degli Studi Di Cagliari.; Italia
Fil: Kisfali, Máté. HUN-REN Institute of Experimental Medicine; Hungría. BiTrial Ltd.; Hungría
Fil: Tóth, Blanka. Budapest University of Technology and Economics; Hungría. Semmelweis University; Hungría
Fil: Ledri, Marco. HUN-REN Institute of Experimental Medicine; Hungría. Lund University; Suecia
Fil: Vizi, E. Sylvester. HUN-REN Institute of Experimental Medicine; Hungría
Fil: Melis, Miriam. Università Degli Studi Di Cagliari.; Italia
Fil: Barna, László. Indiana University; Estados Unidos
Fil: Lenkei, Zsolt. Inserm; Francia
Fil: Soltész, Iván. University of Stanford; Estados Unidos
Fil: Katona, István. Indiana University; Estados Unidos. HUN-REN Institute of Experimental Medicine; Hungría
description While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB1Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ9-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell–dependent manner.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/240036
Barti, Benjámin; Dudok, Barna; Kenesei, Kata; Zöldi, Miklós; Miczán, Vivien; et al.; Presynaptic nanoscale components of retrograde synaptic signaling; Science Advances is the American Association for the Advancement of Science; Science Advances; 10; 22; 5-2024; 1-20
2375-2548
CONICET Digital
CONICET
url http://hdl.handle.net/11336/240036
identifier_str_mv Barti, Benjámin; Dudok, Barna; Kenesei, Kata; Zöldi, Miklós; Miczán, Vivien; et al.; Presynaptic nanoscale components of retrograde synaptic signaling; Science Advances is the American Association for the Advancement of Science; Science Advances; 10; 22; 5-2024; 1-20
2375-2548
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.ado0077
info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ado0077
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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