National Academy of Sciences, Proceedings of the National Academy of Sciences, 40(117), p. 25085-25091, 2020
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Significance AMPA receptors (AMPARs) are the principle postsynaptic glutamate receptors mediating fast excitatory synaptic transmission in the brain. Regulation of synaptic AMPAR expression is required for the expression of synaptic plasticity and normal brain function. The turnover of AMPARs within synapses is highly dynamic, and the molecular mechanisms underlying AMPAR trafficking remain unclear. Here we report that GRIP1, an AMPAR-binding protein, plays an essential role in delivering AMPAR into synapses during synaptic plasticity, particularly in long-term potentiation. In addition, the deletion of Grip1 causes synaptic plasticity deficits and impaired learning and memory. Our study reveals a mechanism through which GRIP1 regulates AMPAR trafficking and impacts activity-dependent synaptic strengthening, as well as learning and memory.