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

在这项研究中，我们研究了SPAL-1的生理作用，一种新的GAP的RAP-1/2，使用SPAL-1缺陷小鼠。特别是，我们重点研究了NMDA受体/PSD-95/SPAL-1相互作用在突触可塑性中的意义. SPAL-1基因缺陷小鼠在Morris水迷宫实验中表现出空间学习障碍，在恐惧条件反射实验中表现出线索恐惧反应降低。这一发现表明，SPAL-1参与海马或杏仁核依赖的记忆形成.我们发现SPAL-1缺失的小鼠条件性眨眼反应受损，提示SPAL-1与NMDA受体之间存在功能联系.海马脑片电生理分析显示SPAL-1缺陷小鼠海马CA 1区LTP增强.脑切片的电子显微镜分析显示，缺乏SPAL-1.5的小鼠的棘更小，PSD更短。我们进一步研究了SPAL-1缺陷小鼠的行为特征，并在旷场试验中发现运动活性增加。

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.