Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation

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Abstract
To monitor changes in α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP). This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons. In dendrites visualized with two-photon laser scanning microscopy or electron microscopy, most of the GluR1-GFP was intracellular, mimicking endogenous GluR1 distribution. Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites. These postsynaptic trafficking events required synapticN-methyl-d-aspartate (NMDA) receptor activation and may contribute to the enhanced AMPA receptor–mediated transmission observed during long-term potentiation and activity-dependent synaptic maturation.