SNX27 Regulates Synaptic Transmission And Plasticity

Objective:Among sorting nexin family proteins,SNX27 is a unique one as it plays crucial role in sorting and recycling transmembrane proteins from endosome-to-plasma membrane.SNX27 deficiency disrupts trafficking of synaptic receptors and leads to synaptic dysfunction.In this study,we will determine the functions of SNX27 using aSNX27 transgenic mouse model.Method:In order to study SNX27's function in vivo,we generated a SNX27 transgenic mouse model in which human SNX27 transgene is driven by a CamK2a promoter.Immunoblot analysis indicates that SNX27 transgene is specifically expressed in cortical and hippocampal regions but not in cerebellum.To determine whether SNX27 overexpression affects pre-or post-synaptic function,we recorded mini-excitatory/inhibitory postsynaptic current(mEPSC/mIPSC)in CA1 pyramidal neurons.In addition,basal synaptic transmission was examined by input/output(I/O)and paired pulse ratio(PPR).In order to evaluate whether SNX27 overexpression affects synaptic plasticity,we recorded long-term potentiation(LTP).To ascertain whether SNX27 transgenic mice display epilepsy-like phenotype,we also performed EEG recording.Results:mEPSC recoding shows that SNX27 transgenic mice have higher postsynaptic response capability than their WT littermates,however,it seems that presynaptic function was not compromised in SNX27 transgenic mice,this has also been proved by unchanged PPR.Higher Schaffer collateral pathway LTP in SNX27 transgenic mice indicates enhanced function of CA3-CA1 neural circuit.Although SNX27 transgenic mice show enhanced excitatory synaptic function,our EEG recording displays a relatively normal pattern in SNX27 transgenic mice.Conclusion:Electrophysiological recording indicates that SNX27 overexpression enhances LTP and excitatory synaptic function;EEG recording suggests that SNX27 transgenic mice did not show epilepsy-like phenotypes.In summary,SNX27 overexpression strengthens synaptic function,learning and memory,but may not affect excitatory-inhibitory balance in SNX27 transgenic mouse cortex.