Effects Of NMDAR Membrane Trafficking In Synaptic Plasticity And Learning And Memory

N-methyl-D-aspartate receptors(N-methyl-D-aspartate receptor,NMDA)are subclasses of ionic glutamate receptors that are involved in numerous brain physiological and pathological functions.In the process of synaptic plasticity,it is generally believed that NMDA receptors mainly play a role similar to "switching" in the induction stage.When synaptic plasticity occurs,the activation and opening of NMDA receptors causes the influx of calcium ions,and the upper membrane of AMPA receptors(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor,AMPA)is opened through a series of downstream signaling pathways,which increases the number of AMPA receptors in the postsynaptic membrane and promotes the expression of plasticity.The induction of synaptic plasticity can also promote the trafficking of NMDA receptors to the upper membrane,enhance the intensity of NMDA receptor-mediated currents,and produce the phenomenon of long-term enhancement(LTP)of NMDA receptor-mediated currents.However,the exact physiological role of NMDA receptor membrane trafficking in brain function that occurs with synaptic plasticity remains unclear.In this master’s thesis,whole-cell patch clamp and field potential recording techniques were used to interfere with the membrane transport process of NMDA receptors in post-synaptic membranes on acute hippocampal tablet specimens,and its effects on a variety of classical plasticity and various hippocampal-related memory behaviors were observed.The study found that the mutation of the 293-locus serine point of the NMDA receptors trafficking key protein SAP97 to non-phosphorylated alanine was able to inhibit the activity-dependent membrane trafficking process of the NMDA receptor and block the NMDA receptor-mediated current LTP.It is worth noting that this inhibition of NMDA receptor membrane trafficking also inhibits AMPA receptor membrane transport and the generation of a variety of classical LTPs it mediates.In view of the important role of synaptic plasticity in learning and memory,we further observed the role of NMDA receptor membrane trafficking in learning and memory,and found that inhibition of NMDA receptor membrane trafficking in the dorsal hippocampus of rats had different effects on hippocampal-related novel object recognition,object location task and temporal order memory task.Our findings suggest that activity-dependent NMDA receptor membrane transport plays an important role in synaptic plasticity and learning memory.These results provide an important experimental basis for further exploring the molecular mechanisms of NMDA receptor membrane transport affecting synaptic plasticity and learning and memory.