The maintenance of synaptic changes resulting from long-term potentiation (LTP) is essential for brain functions. Different LTP phases have been associated with diverse molecular processes and pathways, and the molecular underpinnings of LTP on the time scales of a few minutes or of several hours are well established. However, the principles underlying the maintenance of the early phase of LTP (E-LTP) on the intermediate time scale of 1-6 hours remains elusive. We hypothesize that specific features of postsynaptic receptor trafficking would be responsible for sustaining synaptic changes during this LTP phase. We test this hypothesis by formalizing a biophysical model that integrates several experimentally-motivated mechanisms. The model captures a wide range of experimental findings and predicts that synaptic changes are preserved for hours when the receptor dynamics are shaped by the interplay of structural changes of the spine in conjunction with increased trafficking from recycling endosomes and the cooperative binding of receptors. Furthermore, our model provides several predictions to verify experimentally our findings.
bioRxiv Subject Collection: Neuroscience