Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex

Autores
Lee, Gloria S.; Graham, Devon L.; Noble, Brenda L.; Trammell, Taylor S.; McCarthy, Deirdre M.; Anderson, Lisa R.; Rubinstein, Marcelo; Bhide, Pradeep G.; Stanwood, Gregg D.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.
Fil: Lee, Gloria S.. Florida State University; Estados Unidos
Fil: Graham, Devon L.. Florida State University; Estados Unidos
Fil: Noble, Brenda L.. Florida State University; Estados Unidos
Fil: Trammell, Taylor S.. Florida State University; Estados Unidos
Fil: McCarthy, Deirdre M.. Florida State University; Estados Unidos
Fil: Anderson, Lisa R.. Florida State 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: Bhide, Pradeep G.. Florida State University; Estados Unidos
Fil: Stanwood, Gregg D.. Florida State University; Estados Unidos
Materia
CEREBRAL CORTEX
CONDITIONAL KNOCKOUT
D2 RECEPTOR
DRD2
INTERNEURON
MK-801
MOTOR LEARNING
PARVALBUMIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/201403
Acceder
id CONICETDig_78fd2552fc44d31be673ccd1677100f0
oai_identifier_str oai:ri.conicet.gov.ar:11336/201403
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortexLee, Gloria S.Graham, Devon L.Noble, Brenda L.Trammell, Taylor S.McCarthy, Deirdre M.Anderson, Lisa R.Rubinstein, MarceloBhide, Pradeep G.Stanwood, Gregg D.CEREBRAL CORTEXCONDITIONAL KNOCKOUTD2 RECEPTORDRD2INTERNEURONMK-801MOTOR LEARNINGPARVALBUMINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.Fil: Lee, Gloria S.. Florida State University; Estados UnidosFil: Graham, Devon L.. Florida State University; Estados UnidosFil: Noble, Brenda L.. Florida State University; Estados UnidosFil: Trammell, Taylor S.. Florida State University; Estados UnidosFil: McCarthy, Deirdre M.. Florida State University; Estados UnidosFil: Anderson, Lisa R.. Florida State 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: Bhide, Pradeep G.. Florida State University; Estados UnidosFil: Stanwood, Gregg D.. Florida State University; Estados UnidosFrontiers Media2022-01-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201403Lee, Gloria S.; Graham, Devon L.; Noble, Brenda L.; Trammell, Taylor S.; McCarthy, Deirdre M.; et al.; Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex; Frontiers Media; Frontiers in Behavioral Neuroscience; 15; 815713; 13-1-2022; 1-251662-5153CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fnbeh.2021.815713info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnbeh.2021.815713/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:52Zoai:ri.conicet.gov.ar:11336/201403instacron: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 09:58:52.92CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
title Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
spellingShingle Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
Lee, Gloria S.
CEREBRAL CORTEX
CONDITIONAL KNOCKOUT
D2 RECEPTOR
DRD2
INTERNEURON
MK-801
MOTOR LEARNING
PARVALBUMIN
title_short Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
title_full Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
title_fullStr Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
title_full_unstemmed Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
title_sort Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
dc.creator.none.fl_str_mv Lee, Gloria S.
Graham, Devon L.
Noble, Brenda L.
Trammell, Taylor S.
McCarthy, Deirdre M.
Anderson, Lisa R.
Rubinstein, Marcelo
Bhide, Pradeep G.
Stanwood, Gregg D.
author Lee, Gloria S.
author_facet Lee, Gloria S.
Graham, Devon L.
Noble, Brenda L.
Trammell, Taylor S.
McCarthy, Deirdre M.
Anderson, Lisa R.
Rubinstein, Marcelo
Bhide, Pradeep G.
Stanwood, Gregg D.
author_role author
author2 Graham, Devon L.
Noble, Brenda L.
Trammell, Taylor S.
McCarthy, Deirdre M.
Anderson, Lisa R.
Rubinstein, Marcelo
Bhide, Pradeep G.
Stanwood, Gregg D.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CEREBRAL CORTEX
CONDITIONAL KNOCKOUT
D2 RECEPTOR
DRD2
INTERNEURON
MK-801
MOTOR LEARNING
PARVALBUMIN
topic CEREBRAL CORTEX
CONDITIONAL KNOCKOUT
D2 RECEPTOR
DRD2
INTERNEURON
MK-801
MOTOR LEARNING
PARVALBUMIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.
Fil: Lee, Gloria S.. Florida State University; Estados Unidos
Fil: Graham, Devon L.. Florida State University; Estados Unidos
Fil: Noble, Brenda L.. Florida State University; Estados Unidos
Fil: Trammell, Taylor S.. Florida State University; Estados Unidos
Fil: McCarthy, Deirdre M.. Florida State University; Estados Unidos
Fil: Anderson, Lisa R.. Florida State 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: Bhide, Pradeep G.. Florida State University; Estados Unidos
Fil: Stanwood, Gregg D.. Florida State University; Estados Unidos
description Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.
publishDate 2022
dc.date.none.fl_str_mv 2022-01-13
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/11336/201403
Lee, Gloria S.; Graham, Devon L.; Noble, Brenda L.; Trammell, Taylor S.; McCarthy, Deirdre M.; et al.; Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex; Frontiers Media; Frontiers in Behavioral Neuroscience; 15; 815713; 13-1-2022; 1-25
1662-5153
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201403
identifier_str_mv Lee, Gloria S.; Graham, Devon L.; Noble, Brenda L.; Trammell, Taylor S.; McCarthy, Deirdre M.; et al.; Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex; Frontiers Media; Frontiers in Behavioral Neuroscience; 15; 815713; 13-1-2022; 1-25
1662-5153
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fnbeh.2021.815713
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnbeh.2021.815713/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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 13.070432

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