Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism

Autores
Sanchez, Gonzalo Manuel; Rodriguez, Mariano Julian; Pomata, Pablo Ernesto; Rela, Lorena; Murer, Mario Gustavo
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response toappetitiveand aversiveeventsandtoenvironmentalcuesthathavepredicted these eventsduringlearning. Notably,thepause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of IsAHP, a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that IsAHP induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces IsAHP and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, areduction ofIsAHPmay alter synchronization ofcholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.© 2011 the authors.
Fil: Sanchez, Gonzalo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Rodriguez, Mariano Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pomata, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
STRIATUM
CHOLINERGIC INTERNEURONS
TONICALLY ACTIVE NEURONS
PARKINSON'S DISEASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/52028
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52028
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonismSanchez, Gonzalo ManuelRodriguez, Mariano JulianPomata, Pablo ErnestoRela, LorenaMurer, Mario GustavoSTRIATUMCHOLINERGIC INTERNEURONSTONICALLY ACTIVE NEURONSPARKINSON'S DISEASEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response toappetitiveand aversiveeventsandtoenvironmentalcuesthathavepredicted these eventsduringlearning. Notably,thepause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of IsAHP, a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that IsAHP induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces IsAHP and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, areduction ofIsAHPmay alter synchronization ofcholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.© 2011 the authors.Fil: Sanchez, Gonzalo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Rodriguez, Mariano Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pomata, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaSociety for Neuroscience2011-04info: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/11336/52028Sanchez, Gonzalo Manuel; Rodriguez, Mariano Julian; Pomata, Pablo Ernesto; Rela, Lorena; Murer, Mario Gustavo; Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism; Society for Neuroscience; Journal of Neuroscience; 31; 17; 4-2011; 6553-65640270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.6345-10.2011info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/31/17/6553info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:13Zoai:ri.conicet.gov.ar:11336/52028instacron: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:34982025-09-29 09:43:13.497CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
title Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
spellingShingle Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
Sanchez, Gonzalo Manuel
STRIATUM
CHOLINERGIC INTERNEURONS
TONICALLY ACTIVE NEURONS
PARKINSON'S DISEASE
title_short Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
title_full Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
title_fullStr Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
title_full_unstemmed Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
title_sort Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism
dc.creator.none.fl_str_mv Sanchez, Gonzalo Manuel
Rodriguez, Mariano Julian
Pomata, Pablo Ernesto
Rela, Lorena
Murer, Mario Gustavo
author Sanchez, Gonzalo Manuel
author_facet Sanchez, Gonzalo Manuel
Rodriguez, Mariano Julian
Pomata, Pablo Ernesto
Rela, Lorena
Murer, Mario Gustavo
author_role author
author2 Rodriguez, Mariano Julian
Pomata, Pablo Ernesto
Rela, Lorena
Murer, Mario Gustavo
author2_role author
author
author
author
dc.subject.none.fl_str_mv STRIATUM
CHOLINERGIC INTERNEURONS
TONICALLY ACTIVE NEURONS
PARKINSON'S DISEASE
topic STRIATUM
CHOLINERGIC INTERNEURONS
TONICALLY ACTIVE NEURONS
PARKINSON'S DISEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response toappetitiveand aversiveeventsandtoenvironmentalcuesthathavepredicted these eventsduringlearning. Notably,thepause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of IsAHP, a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that IsAHP induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces IsAHP and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, areduction ofIsAHPmay alter synchronization ofcholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.© 2011 the authors.
Fil: Sanchez, Gonzalo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Rodriguez, Mariano Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pomata, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description Striatal cholinergic interneurons show tonic spiking activity in the intact and sliced brain, which stems from intrinsic mechanisms. Because of it, they are also known as "tonically active neurons" (TANs). Another hallmark of TAN electrophysiology is a pause response toappetitiveand aversiveeventsandtoenvironmentalcuesthathavepredicted these eventsduringlearning. Notably,thepause response is lost after the degeneration of dopaminergic neurons in animal models of Parkinson's disease. Moreover, Parkinson's disease patients are in a hypercholinergic state and find some clinical benefit in anticholinergic drugs. Current theories propose that excitatory thalamic inputs conveying information about salient sensory stimuli trigger an intrinsic hyperpolarizing response in the striatal cholinergic interneurons. Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of IsAHP, a slow outward current that mediates an afterhyperpolarization following a train of action potentials. Here we report that IsAHP induces a marked spike-frequency adaptation in adult rat striatal cholinergic interneurons, inducing an abrupt end of firing during sustained excitation. Chronic loss of dopaminergic neurons markedly reduces IsAHP and spike-frequency adaptation in cholinergic interneurons, allowing them to fire continuously and at higher rates during sustained excitation. These findings provide a plausible explanation for the hypercholinergic state in Parkinson's disease. Moreover, areduction ofIsAHPmay alter synchronization ofcholinergic interneurons with afferent inputs, thus contributing to the loss of the pause response in Parkinson's disease.© 2011 the authors.
publishDate 2011
dc.date.none.fl_str_mv 2011-04
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/11336/52028
Sanchez, Gonzalo Manuel; Rodriguez, Mariano Julian; Pomata, Pablo Ernesto; Rela, Lorena; Murer, Mario Gustavo; Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism; Society for Neuroscience; Journal of Neuroscience; 31; 17; 4-2011; 6553-6564
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52028
identifier_str_mv Sanchez, Gonzalo Manuel; Rodriguez, Mariano Julian; Pomata, Pablo Ernesto; Rela, Lorena; Murer, Mario Gustavo; Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism; Society for Neuroscience; Journal of Neuroscience; 31; 17; 4-2011; 6553-6564
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.6345-10.2011
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/31/17/6553
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
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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