University of Bordeaux, CNRS, IINS, UMR 5297, 33000 Bordeaux, France.
University of Bordeaux, CNRS, IINS, UMR 5297, 33000 Bordeaux, France.
Neuron. 2023 Aug 2;111(15):2312-2328. doi: 10.1016/j.neuron.2023.05.002. Epub 2023 May 25.
N-Methyl-D-aspartate ionotropic glutamate receptors (NMDARs) play key roles in synaptogenesis, synaptic maturation, long-term plasticity, neuronal network activity, and cognition. Mirroring this wide range of instrumental functions, abnormalities in NMDAR-mediated signaling have been associated with numerous neurological and psychiatric disorders. Thus, identifying the molecular mechanisms underpinning the physiological and pathological contributions of NMDAR has been a major area of investigation. Over the past decades, a large body of literature has flourished, revealing that the physiology of ionotropic glutamate receptors cannot be restricted to fluxing ions, and involves additional facets controlling synaptic transmissions in health and disease. Here, we review newly discovered dimensions of postsynaptic NMDAR signaling supporting neural plasticity and cognition, such as the nanoscale organization of NMDAR complexes, their activity-dependent redistributions, and non-ionotropic signaling capacities. We also discuss how dysregulations of these processes may directly contribute to NMDAR-dysfunction-related brain diseases.
N-甲基-D-天冬氨酸离子型谷氨酸受体（NMDARs）在突触发生、突触成熟、长期可塑性、神经元网络活动和认知中发挥着关键作用。与这种广泛的功能相呼应，NMDAR 介导的信号异常与许多神经和精神疾病有关。因此，确定 NMDAR 的生理和病理贡献的分子机制一直是一个主要的研究领域。在过去的几十年中，大量的文献蓬勃发展，揭示了离子型谷氨酸受体的生理学不能仅限于离子通量，还涉及控制健康和疾病中突触传递的其他方面。在这里，我们回顾了新发现的支持神经可塑性和认知的突触后 NMDAR 信号的维度，例如 NMDAR 复合物的纳米级组织、它们的活动依赖性重分布以及非离子型信号转导能力。我们还讨论了这些过程的失调如何直接导致与 NMDAR 功能障碍相关的脑部疾病。
