Artículo
Dopamine D 4 Receptor-Deficient Mice Display Cortical Hyperexcitability
Rubinstein, Marcelo
; Cepeda, Carlos; Hurst, Raymond S.; Flores Hernandez, Jorge; Ariano, Marjorie A.; Falzone, Tomas Luis
; Kozell, Laura B.; Meshul, Charles K.; Bunzow, James R.; Low, Malcolm J.; Levine, Michael S.; Grandy, David K.
Fecha de publicación:
06/2001
Editorial:
Society for Neuroscience
Revista:
Journal of Neuroscience
ISSN:
0270-6474
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D(4)R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and voltage-clamp recordings were performed in cortical pyramidal neurons from wild-type and D(4)R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D(4)R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D(4)R can function as an inhibitory modulator of glutamate activity in the FC.
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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"
Citación
Rubinstein, Marcelo; Cepeda, Carlos; Hurst, Raymond S.; Flores Hernandez, Jorge; Ariano, Marjorie A.; et al.; Dopamine D 4 Receptor-Deficient Mice Display Cortical Hyperexcitability; Society for Neuroscience; Journal of Neuroscience; 21; 11; 6-2001; 3756-3763
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