Regulation of synaptic function by NMDA receptor/PSD-95/SPAL-1 complex

在这项研究中，我们使用SPAL-1缺陷小鼠研究了SPAL-1的生理作用，SPAL-1是rap1 /2的一种新的GAP。我们特别关注了NMDA受体/PSD-95/SPAL-1相互作用在突触可塑性中的意义。在Morris水迷宫实验中，spal -1缺失小鼠空间学习能力受损，在恐惧条件反射实验中，提示恐惧反应减弱。这一发现表明SPAL-1参与了海马或杏仁核依赖性记忆的形成。我们发现缺乏SPAL-1的小鼠条件眨眼反应受损，表明SPAL-1与NMDA受体之间存在功能联系。电生理分析显示spal -1缺失小鼠海马CA1区LTP增强。脑切片电镜分析显示SPAL-1.5缺失小鼠的脊柱更小，PSD更短。我们进一步研究了spal -1缺陷小鼠的行为特征，发现在空地测试中运动活动增加。

In this study, we examined physiological roles of SPAL-1, a novel GAP for Rap-1/2, using SPAL-1-deficient mice. In particular, we focused on the significance of NMDA receptor/PSD-95/SPAL-1 interaction in synaptic plasticity.1. SPAL-1-deficient mice showed impaired spatial learning in Morris water maze test and decreased cued fear response in fear conditioning test. This finding suggests that SPAL-1 is involved in hippocampus- or amygdale-dependent memory formation.2. We found that conditioned eyeblink response is impaired in mice lacking SPAL-1, suggesting that functional link between SPAL-1 and NMDA receptors.3. Electrophysiological analysis using hippocampal slices revealed enhanced LTP in hippocampal CA1 region in SPAL-1-deficient mice.4. Electron microscopic analysis of brain sections revealed smaller spines and shorter PSD in mice lacking SPAL-1.5. We further investigated the behavioral characteristics of SPAL-1-deficient mice and found increased locomotor activity in the open-field test.