Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD.
Recycling endosomes supply AMPA receptors for LTP.
Science. 2004 Sep 24;305(5692):1972-5.
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This new study from the Ehlers and Kauer groups provides important new insight into the molecular mechanisms underlying the expression of long-term potentiation (LTP), the principal cellular model for learning and memory. Prior work has established that insertion of AMPA receptors into the postsynaptic membrane (a process termed "AMPAfication") is the major molecular event mediating the increase in synaptic strength in LTP. As a result, so-called "silent synapses" bearing NMDARs but lacking AMPARs are converted to functional synapses exhibiting AMPAR-dependent transmission. However, the source of newly inserted AMPARs in LTP was previously unknown. The present study shows convincingly that these AMPARs are derived from a reserve pool of recycling endosomes, and that NMDAR activation during LTP induction elicits rapid mobilization of this pool for transport of AMPARs and other endosomal cargo to the plasma membrane. These findings demonstrate a key role for trafficking of recycling endosomes in experience-dependent changes in synaptic strength. It will now be important to determine how synaptic activity regulates the molecular machinery involved in endosomal trafficking, and these mechanisms may provide novel approaches for the pharmacological enhancement of LTP and memory.
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