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Involucramiento del receptor de N-metil D-aspartato (NMDA) en la eliminación de sinapsis durante el desarrollo

S Rabacchi¹, Y Bailly, N Delhaye-Bouchaud

¹Université Pierre and Marie Curie, Institut des Neurosciences, Paris, France.

Science (New York, N.Y.)

|June 26, 1992

Resumen

El receptor de N-metil D-aspartato (NMDA) es crucial para la eliminación de sinapsis durante el desarrollo del cerebro. El bloqueo de los receptores NMDA con D,L-APV impidió la eliminación del exceso de sinapsis en el desarrollo del cerebelo de la rata.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología del desarrollo Biología del desarrollo.
Neurofisiología La neurofisiología.

Sus antecedentes:

Las conexiones neuronales se refinan durante el desarrollo a través de procesos como la poda axonal y la eliminación de sinapsis.
Se conoce el papel de los receptores de N-metil D-aspartato (NMDA) en la configuración del árbol axonal, pero su papel en la estabilización de las sinapsis no está claro.
Comprender la eliminación de sinapsis es clave para comprender la formación de circuitos neuronales.

Objetivo del estudio:

Investigar el papel de la activación del receptor NMDA en la eliminación de sinapsis funcionales durante el desarrollo cerebeloso.
Para determinar si el bloqueo de los receptores NMDA afecta la eliminación de la sinapsis in vivo.

Principales métodos:

Administración crónica in vivo de ácido D,L-2-amino-5-fosfonovalérico (D,L-APV), un antagonista selectivo del receptor NMDA.
Análisis de la eliminación de sinapsis en el cerebelo en desarrollo de la rata, centrándose específicamente en las células de Purkinje y las sinapsis de fibra trepadora.
Comparación de los efectos entre el isómero activo D,L-APV y el isómero inactivo L-APV.

Principales resultados:

El tratamiento con D,L-APV inhibió significativamente la regresión de las sinapsis de fibra de escalada supernumerarias.
Este efecto se observó en el 49% de las células de Purkinje registradas.
El isómero inactivo L-APV no mostró ningún efecto significativo, lo que confirma la especificidad de D,L-APV.

Conclusiones:

La activación del receptor NMDA es un componente crítico del proceso de eliminación de la sinapsis funcional durante el desarrollo.
Dirigirse a los receptores NMDA puede ofrecer información sobre los trastornos neurológicos del desarrollo relacionados con la plasticidad sináptica.
Este estudio pone de relieve la importancia de la señalización mediada por los receptores NMDA en el refinamiento de los circuitos neuronales.

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