Adaptor Protein RIM1 Modulates NMDAR-dependent LTP And Related Behavior In The Mouse Hippocampus

NMDA receptors(NMDARs)are crucial for the excitatory synaptic transmission and synaptic plasticity.The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience,whereas the molecular mechanism mediating NMDARs trafficking remains poorly understood.Here we report that RIM1,with a well-established role in presynaptic vesicle release,also localizes postsynaptically in the mouse hippocampus.Postsynaptic RIM1 in the hippocampal CA1 region is required for basal NMDAR-,but not AMPA receptor(AMPAR)-,mediated synaptic responses,along with contributions to synaptic plasticity and hippocampus-dependent memory.In this study,we also explore the role of Rab11-FIP3,an effector of small G protein Rab11 which is involved in endosomal recycling,in NMDAR-dependent plasticity.Rab11-FIP3 is involved in the complex of NMDA receptors but does not interact with AMPA receptors.Knockdown of Rabll-FIP3 in the hippocampal CA1 region impairs NMDA receptor-dependent LTP but does not affect the basic synaptic transmission.Together,this study identified two postsynaptic adaptor proteins RIM1 and FIP3 that specifically participate in the synaptic function of NMDA receptors and affect the NMDA receptor-mediated synaptic plasticity.