Minister of Education (MOE) Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, Jiangsu Province 210096, China.
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Shanghai Medical School of Fudan University, Shanghai 200032, China.
Cell Rep. 2022 Aug 16;40(7):111217. doi: 10.1016/j.celrep.2022.111217.
NMDA receptor (NMDAR) plays a vital role in brain development and normal physiological functions. Surface trafficking of NMDAR contributes to the modulation of synaptic functions and information processing. However, it remains unclear whether NMDAR trafficking is independent of long-term potentiation (LTP) and whether it regulates behavior. Here, we report that LTP of AMPAR and NMDAR can occur concurrently and that NMDAR trafficking can regulate AMPAR trafficking and AMPAR-mediated LTP. By contrast, AMPAR trafficking does not impact NMDAR-mediated LTP. Using SAP97-interfering peptide and SAP97 knockin (KI) rat, we show that the effect is mediated by GluN2A-subunit-containing NMDARs. At the behavior level, impaired NMDAR trafficking results in deficits in consolidation, but not acquisition, of fear memory. Collectively, our results suggest the essential role of NMDAR trafficking in LTP and memory consolidation.
N-甲基-D-天冬氨酸受体（NMDAR）在大脑发育和正常生理功能中发挥着重要作用。NMDAR 的表面转运有助于调节突触功能和信息处理。然而，目前尚不清楚 NMDAR 的转运是否独立于长时程增强（LTP），以及它是否调节行为。在这里，我们报告 AMPAR 和 NMDAR 的 LTP 可以同时发生，并且 NMDAR 的转运可以调节 AMPAR 的转运和 AMPAR 介导的 LTP。相比之下，AMPAR 的转运不会影响 NMDAR 介导的 LTP。通过使用 SAP97 干扰肽和 SAP97 敲入（KI）大鼠，我们表明这种作用是由含有 GluN2A 亚基的 NMDAR 介导的。在行为水平上，NMDAR 转运受损导致恐惧记忆的巩固而不是获得受损。总的来说，我们的结果表明 NMDAR 转运在 LTP 和记忆巩固中起着重要作用。
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