University de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000, Bordeaux, France.
University de Bordeaux, Interdisciplinary Institute for Neuroscience, CNRS, IINS UMR 5297, Bordeaux, France.
Sci Rep. 2017 Aug 14;7(1):8053. doi: 10.1038/s41598-017-08695-3.
Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging and electrophysiological approaches in hippocampal neurons, that corticosterone specifically controls GluN2B-NMDAR surface dynamics and synaptic content through mineralocorticoid signalling. Strikingly, extracellular corticosterone was sufficient to increase the trapping of GluN2B-NMDAR within synapses. Functionally, corticosterone-induced potentiation of AMPA receptor content in synapses required the changes in NMDAR surface dynamics. These high-resolution imaging data unveiled that, in hippocampal networks, corticosterone is a natural, potent, fast and specific regulator of GluN2B-NMDAR membrane trafficking, tuning NMDAR-dependent synaptic adaptations.
应激激素，如皮质酮，调节海马谷氨酸能突触传递和 NMDA 受体（NMDAR）依赖性突触可塑性，有利于对环境做出明显的行为反应。皮质酮诱导的突触适应性部分依赖于 NMDAR 信号的变化，尽管这种效应的细胞途径仍不清楚。在这里，我们使用海马神经元中的单分子成像和电生理方法证明，皮质酮通过盐皮质激素信号专门控制 GluN2B-NMDAR 的表面动力学和突触含量。引人注目的是，细胞外皮质酮足以增加 GluN2B-NMDAR 在突触内的捕获。功能上，皮质酮诱导的 AMPA 受体含量在突触中的增强需要 NMDAR 表面动力学的变化。这些高分辨率成像数据揭示了，在海马网络中，皮质酮是 GluN2B-NMDAR 膜转运的天然、有效、快速和特异性调节剂，调节 NMDAR 依赖性突触适应性。
