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dc.contributor.author
Lee, Gloria S.
dc.contributor.author
Graham, Devon L.
dc.contributor.author
Noble, Brenda L.
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Trammell, Taylor S.
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McCarthy, Deirdre M.
dc.contributor.author
Anderson, Lisa R.
dc.contributor.author
Rubinstein, Marcelo
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dc.contributor.author
Bhide, Pradeep G.
dc.contributor.author
Stanwood, Gregg D.
dc.date.available
2023-06-26T10:56:46Z
dc.date.issued
2022-01-13
dc.identifier.citation
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
dc.identifier.issn
1662-5153
dc.identifier.uri
http://hdl.handle.net/11336/201403
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CEREBRAL CORTEX
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CONDITIONAL KNOCKOUT
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D2 RECEPTOR
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DRD2
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INTERNEURON
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MK-801
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MOTOR LEARNING
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PARVALBUMIN
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-06-22T10:22:44Z
dc.journal.volume
15
dc.journal.number
815713
dc.journal.pagination
1-25
dc.journal.pais
Suiza
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dc.journal.ciudad
Lausana
dc.description.fil
Fil: Lee, Gloria S.. Florida State University; Estados Unidos
dc.description.fil
Fil: Graham, Devon L.. Florida State University; Estados Unidos
dc.description.fil
Fil: Noble, Brenda L.. Florida State University; Estados Unidos
dc.description.fil
Fil: Trammell, Taylor S.. Florida State University; Estados Unidos
dc.description.fil
Fil: McCarthy, Deirdre M.. Florida State University; Estados Unidos
dc.description.fil
Fil: Anderson, Lisa R.. Florida State University; Estados Unidos
dc.description.fil
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Bhide, Pradeep G.. Florida State University; Estados Unidos
dc.description.fil
Fil: Stanwood, Gregg D.. Florida State University; Estados Unidos
dc.journal.title
Frontiers in Behavioral Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fnbeh.2021.815713
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnbeh.2021.815713/full
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