Artículo
Deletion of dopamine D 2 receptors from parvalbumin interneurons in mouse causes schizophrenialike phenotypes
Tomasella, María Eugenia
; Bechelli, Maria Lucila; Ogando, Mora
; Mininni, Camilo Juan
; Di Guilmi, Mariano Nicolás
; de Fino, Fernanda Teresa
; Zanutto, Bonifacio Silvano
; Elgoyhen, Ana Belen
; Marin Burgin, Antonia
; Gelman, Diego Matias
Fecha de publicación:
03/2018
Editorial:
National Academy of Sciences
Revista:
Proceedings of the National Academy of Sciences of The United States of America
ISSN:
0027-8424
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis. Here, we show that selective dopamine D2 receptor deletion from parvalbumin interneurons in mouse causes an impaired inhibitory activity in the ventral hippocampus and a dysregulated dopaminergic system. Conditional mutant animals show adult onset of schizophrenia-like behaviors and molecular, cellular, and physiological endophenotypes as previously described from postmortem brain studies of patients with schizophrenia. Our findings show that dopamine D2 receptor expression on parvalbumin interneurons is required to modulate and limit pyramidal neuron activity, which may prevent the dysregulation of the dopaminergic system.
Palabras clave:
DELETION
,
DRD2
,
MOUSE
,
PARVALBUMIN
,
PSYCHOSIS
Archivos asociados
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Identificadores
Colecciones
Articulos(IBIOBA - MPSP)
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Citación
Tomasella, María Eugenia; Bechelli, Maria Lucila; Ogando, Mora; Mininni, Camilo Juan; Di Guilmi, Mariano Nicolás; et al.; Deletion of dopamine D 2 receptors from parvalbumin interneurons in mouse causes schizophrenialike phenotypes; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 115; 13; 3-2018; 3476-3481
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