Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition

Acetylcholine (ACh) regulates forms of plasticity that control cognitive functions but the underlying mechanisms remain largely unknown. ACh controls the intrinsic excitability, as well as the synaptic excitation and inhibition of CA1 hippocampal pyramidal cells (PCs), cells known to participate in...

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Detalles Bibliográficos
Autores: Domínguez, Soledad, Fernández de Sevilla García, David, Buño, Washington
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/713824
Acceso en línea:http://hdl.handle.net/10486/713824
https://dx.doi.org/10.1073/pnas.1321777111
Access Level:acceso abierto
Palabra clave:endocannabinoids
LTP of inhibition
outward rectification
Medicina
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spelling Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibitionDomínguez, SoledadFernández de Sevilla García, DavidBuño, WashingtonendocannabinoidsLTP of inhibitionoutward rectificationMedicinaAcetylcholine (ACh) regulates forms of plasticity that control cognitive functions but the underlying mechanisms remain largely unknown. ACh controls the intrinsic excitability, as well as the synaptic excitation and inhibition of CA1 hippocampal pyramidal cells (PCs), cells known to participate in circuits involved in cognition and spatial navigation. However, how ACh regulates inhibition in function of postsynaptic activity has not been well studied. Here we show that in rat PCs, a brief pulse of ACh or a brief stimulation of cholinergic septal fibers combined with repeated depolarization induces strong long-term enhancement of GABAA inhibition (GABAA-LTP). Indeed, this enhanced inhibition is due to the increased activation of α5βγ2 subunit-containing GABAA receptors by the GABA released. GABAA-LTP requires the activation of M1-muscarinic receptors and an increase in cytosolic Ca2+. In the absence of PC depolarization ACh triggered a presynaptic depolarization-induced suppression of inhibition (DSI), revealing that postsynaptic activity gates the effects of ACh from presynaptic DSI to postsynaptic LTP. These results provide key insights into mechanisms potentially linked with cognitive functions, spatial navigation, and the homeostatic control of abnormal hyperexcitable statesThis work was supported by Ministerio de Ciencia and Tecnología Grant BFU2005-07486 and Comunidad Autónoma de Madrid Grant GR/SAL/0877/2004 (to W.B.), and Ministerio de Ciencia e Innovación Grants BFU2008-03488 and BFU2011-23522 (to D.F.d.S.). D.F.d.S. was supported by a Ramón y Cajal Contract and is now a Professor at the Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid. S.D. was a Doctoral Fellow supported by Grant BFU2005-07486 and is now a postdoctoral fellow in the team “Synaptic Plasticity and Neural Networks” at Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8118, at the Université Paris DescartesNational Academy of SciencesDepartamento de Anatomía, Histología y NeurocienciaFacultad de Medicina20142014-07-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/713824https://dx.doi.org/10.1073/pnas.1321777111reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7138242026-06-23T12:46:27Z
dc.title.none.fl_str_mv Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
title Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
spellingShingle Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
Domínguez, Soledad
endocannabinoids
LTP of inhibition
outward rectification
Medicina
title_short Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
title_full Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
title_fullStr Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
title_full_unstemmed Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
title_sort Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABA<inf>A</inf> inhibition
dc.creator.none.fl_str_mv Domínguez, Soledad
Fernández de Sevilla García, David
Buño, Washington
author Domínguez, Soledad
author_facet Domínguez, Soledad
Fernández de Sevilla García, David
Buño, Washington
author_role author
author2 Fernández de Sevilla García, David
Buño, Washington
author2_role author
author
dc.contributor.none.fl_str_mv Departamento de Anatomía, Histología y Neurociencia
Facultad de Medicina
dc.subject.none.fl_str_mv endocannabinoids
LTP of inhibition
outward rectification
Medicina
topic endocannabinoids
LTP of inhibition
outward rectification
Medicina
description Acetylcholine (ACh) regulates forms of plasticity that control cognitive functions but the underlying mechanisms remain largely unknown. ACh controls the intrinsic excitability, as well as the synaptic excitation and inhibition of CA1 hippocampal pyramidal cells (PCs), cells known to participate in circuits involved in cognition and spatial navigation. However, how ACh regulates inhibition in function of postsynaptic activity has not been well studied. Here we show that in rat PCs, a brief pulse of ACh or a brief stimulation of cholinergic septal fibers combined with repeated depolarization induces strong long-term enhancement of GABAA inhibition (GABAA-LTP). Indeed, this enhanced inhibition is due to the increased activation of α5βγ2 subunit-containing GABAA receptors by the GABA released. GABAA-LTP requires the activation of M1-muscarinic receptors and an increase in cytosolic Ca2+. In the absence of PC depolarization ACh triggered a presynaptic depolarization-induced suppression of inhibition (DSI), revealing that postsynaptic activity gates the effects of ACh from presynaptic DSI to postsynaptic LTP. These results provide key insights into mechanisms potentially linked with cognitive functions, spatial navigation, and the homeostatic control of abnormal hyperexcitable states
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-07-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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 http://hdl.handle.net/10486/713824
https://dx.doi.org/10.1073/pnas.1321777111
url http://hdl.handle.net/10486/713824
https://dx.doi.org/10.1073/pnas.1321777111
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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