Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD

The endocytosis of AMPA receptors is thought to be important in the express ion of long-term depression (LTD) triggered by NMDA receptor activation. Al though signaling pathways necessary for LTD induction have been identified, those responsible for the regulated internalization of AMPA receptors are unknown. Here we show that activation of NMDA receptors alone can trigger A MPA receptor endocytosis through calcium influx and activation of the calci um-dependent protein phosphatase calcineurin. A distinct signaling mechanis m mediates the AMPA receptor endocytosis stimulated by insulin. These resul ts demonstrate that although multiple signaling pathways can induce AMPA re ceptor internalization, NMDA receptor activation enhances AMPA receptor end ocytosis via a signaling mechanism required for the induction of LTD.