Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice

Autores
Cepeda, C.; Hurst, R. S.; Altemus, K. L.; Flores Hernández, J.; Calvert, C. R.; Jokel, E. S.; Grandy, David K.; Low, Malcolm J.; Rubinstein, Marcelo; Ariano, M. A.; Levine, M. S.
Año de publicación
2001
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D2 or D4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D2 and D4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D2 receptor-deficient mutants. Bath application of the K+ channel blocker 4-aminopyridine (100 μM) and bicuculline methiodide (10 μM, to block synaptic activity due to activation of GABAA receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D4receptor-deficient mice and their controls. In voltage-clamp recordings, there was an increase in frequency of spontaneous glutamate receptor-mediated inward currents without a change in mean amplitude in D2 receptor-deficient mutants. In WT mice, activation of D2 family receptors with quinpirole decreased spontaneous excitatory events and conversely sulpiride, a D2 receptor antagonist, increased activity. In D2 receptor-deficient mice, sulpiride had very little net effect. Morphologically, a subpopulation of medium-sized spiny neurons from D2 receptor-deficient mice displayed decreased dendritic spines compared with cells from WT mice. These results provide evidence that D2 receptors play an important role in the regulation of glutamate receptor-mediated activity in the corticostriatal or thalamostriatal pathway. These receptors may function as gatekeepers of glutamate release or of its subsequent effects and thus may protect striatal neurons from excessive excitation.
Fil: Cepeda, C.. University of California at Los Angeles; Estados Unidos
Fil: Hurst, R. S.. University of California at Los Angeles; Estados Unidos
Fil: Altemus, K. L.. University of California at Los Angeles; Estados Unidos
Fil: Flores Hernández, J.. University of California at Los Angeles; Estados Unidos
Fil: Calvert, C. R.. University of California at Los Angeles; Estados Unidos
Fil: Jokel, E. S.. University of California at Los Angeles; Estados Unidos
Fil: Grandy, David K.. Oregon Health Sciences University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ariano, M. A.. The Chicago Medical School; Estados Unidos
Fil: Levine, M. S.. University of California at Los Angeles; Estados Unidos
Materia
Dopamina
Corteza Cerebral
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:11336/71785

id CONICETDig_bb2ad9f30fb4b0004259dcd9c4fe7dbd
oai_identifier_str oai:ri.conicet.gov.ar:11336/71785
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient MiceCepeda, C.Hurst, R. S.Altemus, K. L.Flores Hernández, J.Calvert, C. R.Jokel, E. S.Grandy, David K.Low, Malcolm J.Rubinstein, MarceloAriano, M. A.Levine, M. S.DopaminaCorteza Cerebralhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D2 or D4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D2 and D4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D2 receptor-deficient mutants. Bath application of the K+ channel blocker 4-aminopyridine (100 μM) and bicuculline methiodide (10 μM, to block synaptic activity due to activation of GABAA receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D4receptor-deficient mice and their controls. In voltage-clamp recordings, there was an increase in frequency of spontaneous glutamate receptor-mediated inward currents without a change in mean amplitude in D2 receptor-deficient mutants. In WT mice, activation of D2 family receptors with quinpirole decreased spontaneous excitatory events and conversely sulpiride, a D2 receptor antagonist, increased activity. In D2 receptor-deficient mice, sulpiride had very little net effect. Morphologically, a subpopulation of medium-sized spiny neurons from D2 receptor-deficient mice displayed decreased dendritic spines compared with cells from WT mice. These results provide evidence that D2 receptors play an important role in the regulation of glutamate receptor-mediated activity in the corticostriatal or thalamostriatal pathway. These receptors may function as gatekeepers of glutamate release or of its subsequent effects and thus may protect striatal neurons from excessive excitation.Fil: Cepeda, C.. University of California at Los Angeles; Estados UnidosFil: Hurst, R. S.. University of California at Los Angeles; Estados UnidosFil: Altemus, K. L.. University of California at Los Angeles; Estados UnidosFil: Flores Hernández, J.. University of California at Los Angeles; Estados UnidosFil: Calvert, C. R.. University of California at Los Angeles; Estados UnidosFil: Jokel, E. S.. University of California at Los Angeles; Estados UnidosFil: Grandy, David K.. Oregon Health Sciences University; Estados UnidosFil: Low, Malcolm J.. Oregon Health Sciences University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ariano, M. A.. The Chicago Medical School; Estados UnidosFil: Levine, M. S.. University of California at Los Angeles; Estados UnidosAmerican Physiological Society2001-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71785Cepeda, C.; Hurst, R. S.; Altemus, K. L.; Flores Hernández, J.; Calvert, C. R.; et al.; Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice; American Physiological Society; Journal of Neurophysiology; 85; 2; 2-2001; 659-6700022-3077CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/jn.2001.85.2.659info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/jn.2001.85.2.659info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:11Zoai:ri.conicet.gov.ar:11336/71785instacron: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 09:53:12.128CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
title Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
spellingShingle Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
Cepeda, C.
Dopamina
Corteza Cerebral
title_short Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
title_full Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
title_fullStr Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
title_full_unstemmed Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
title_sort Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice
dc.creator.none.fl_str_mv Cepeda, C.
Hurst, R. S.
Altemus, K. L.
Flores Hernández, J.
Calvert, C. R.
Jokel, E. S.
Grandy, David K.
Low, Malcolm J.
Rubinstein, Marcelo
Ariano, M. A.
Levine, M. S.
author Cepeda, C.
author_facet Cepeda, C.
Hurst, R. S.
Altemus, K. L.
Flores Hernández, J.
Calvert, C. R.
Jokel, E. S.
Grandy, David K.
Low, Malcolm J.
Rubinstein, Marcelo
Ariano, M. A.
Levine, M. S.
author_role author
author2 Hurst, R. S.
Altemus, K. L.
Flores Hernández, J.
Calvert, C. R.
Jokel, E. S.
Grandy, David K.
Low, Malcolm J.
Rubinstein, Marcelo
Ariano, M. A.
Levine, M. S.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dopamina
Corteza Cerebral
topic Dopamina
Corteza Cerebral
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D2 or D4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D2 and D4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D2 receptor-deficient mutants. Bath application of the K+ channel blocker 4-aminopyridine (100 μM) and bicuculline methiodide (10 μM, to block synaptic activity due to activation of GABAA receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D4receptor-deficient mice and their controls. In voltage-clamp recordings, there was an increase in frequency of spontaneous glutamate receptor-mediated inward currents without a change in mean amplitude in D2 receptor-deficient mutants. In WT mice, activation of D2 family receptors with quinpirole decreased spontaneous excitatory events and conversely sulpiride, a D2 receptor antagonist, increased activity. In D2 receptor-deficient mice, sulpiride had very little net effect. Morphologically, a subpopulation of medium-sized spiny neurons from D2 receptor-deficient mice displayed decreased dendritic spines compared with cells from WT mice. These results provide evidence that D2 receptors play an important role in the regulation of glutamate receptor-mediated activity in the corticostriatal or thalamostriatal pathway. These receptors may function as gatekeepers of glutamate release or of its subsequent effects and thus may protect striatal neurons from excessive excitation.
Fil: Cepeda, C.. University of California at Los Angeles; Estados Unidos
Fil: Hurst, R. S.. University of California at Los Angeles; Estados Unidos
Fil: Altemus, K. L.. University of California at Los Angeles; Estados Unidos
Fil: Flores Hernández, J.. University of California at Los Angeles; Estados Unidos
Fil: Calvert, C. R.. University of California at Los Angeles; Estados Unidos
Fil: Jokel, E. S.. University of California at Los Angeles; Estados Unidos
Fil: Grandy, David K.. Oregon Health Sciences University; Estados Unidos
Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ariano, M. A.. The Chicago Medical School; Estados Unidos
Fil: Levine, M. S.. University of California at Los Angeles; Estados Unidos
description Dopamine (DA) receptors play an important role in the modulation of excitability and the responsiveness of neurons to activation of excitatory amino acid receptors in the striatum. In the present study, we utilized mice with genetic deletion of D2 or D4 DA receptors and their wild-type (WT) controls to examine if the absence of either receptor subtype affects striatal excitatory synaptic activity. Immunocytochemical analysis verified the absence of D2 or D4 protein expression in the striatum of receptor-deficient mutant animals. Sharp electrode current- and whole cell patch voltage-clamp recordings were obtained from slices of receptor-deficient and WT mice. Basic membrane properties were similar in D2 and D4 receptor-deficient mutants and their respective WT controls. In current-clamp recordings in WT animals, very little low-amplitude spontaneous synaptic activity was observed. The frequency of these spontaneous events was increased slightly in D2 receptor-deficient mice. In addition, large-amplitude depolarizations were observed in a subset of neurons from only the D2 receptor-deficient mutants. Bath application of the K+ channel blocker 4-aminopyridine (100 μM) and bicuculline methiodide (10 μM, to block synaptic activity due to activation of GABAA receptors) markedly increased spontaneous synaptic activity in receptor-deficient mutants and WTs. Under these conditions, D2 receptor-deficient mice displayed significantly more excitatory synaptic activity than their WT controls, while there was no difference between D4receptor-deficient mice and their controls. In voltage-clamp recordings, there was an increase in frequency of spontaneous glutamate receptor-mediated inward currents without a change in mean amplitude in D2 receptor-deficient mutants. In WT mice, activation of D2 family receptors with quinpirole decreased spontaneous excitatory events and conversely sulpiride, a D2 receptor antagonist, increased activity. In D2 receptor-deficient mice, sulpiride had very little net effect. Morphologically, a subpopulation of medium-sized spiny neurons from D2 receptor-deficient mice displayed decreased dendritic spines compared with cells from WT mice. These results provide evidence that D2 receptors play an important role in the regulation of glutamate receptor-mediated activity in the corticostriatal or thalamostriatal pathway. These receptors may function as gatekeepers of glutamate release or of its subsequent effects and thus may protect striatal neurons from excessive excitation.
publishDate 2001
dc.date.none.fl_str_mv 2001-02
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/11336/71785
Cepeda, C.; Hurst, R. S.; Altemus, K. L.; Flores Hernández, J.; Calvert, C. R.; et al.; Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice; American Physiological Society; Journal of Neurophysiology; 85; 2; 2-2001; 659-670
0022-3077
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71785
identifier_str_mv Cepeda, C.; Hurst, R. S.; Altemus, K. L.; Flores Hernández, J.; Calvert, C. R.; et al.; Facilitated Glutamatergic Transmission in the Striatum of D 2 Dopamine Receptor-Deficient Mice; American Physiological Society; Journal of Neurophysiology; 85; 2; 2-2001; 659-670
0022-3077
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/jn.2001.85.2.659
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/jn.2001.85.2.659
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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
_version_ 1842269207683661824
score 13.13397