The Roles of NR2A and NR2B in Long-Term Plasticity

描述(申请人提供)：长时程增强(LTP)和长时程增强(LTD)是突触强度的持久的、活动相关的变化，已被认为是学习和记忆的基础。这些形式的可塑性依赖于NMDA受体的激活，最近的研究表明，这些NMDA受体的亚单位组成(特别是受体复合体是否包含NR2A和NR2B亚单位)在它们的激活是否导致LTP或LTD中起着重要作用。然而，这些研究主要是药理学的，提供了相互矛盾的结果，他们的结论仍然有一些争议。这项建议的第一个目的是使用药理拮抗剂来确定NR2A和NR2B在长期可塑性中的作用是否随着发育而改变。第二个目的是研究这些亚基除了作为受体通道的作用外，还作为分子支架的作用。这将通过评估使用RNAi降低NR2A和NR2B表达对LTP和LTD的影响来完成。第三个目的是增加光剥夺大鼠视皮质中NR2A的表达，以研究NR2A在经验依赖性可塑性中的作用。

DESCRIPTION (provided by applicant): Long-term potentiation (LTP) and long-term depression (LTD) are lasting, activity-dependent changes in synaptic strength that have been proposed to underlie learning and memory. These forms of plasticity are dependent on NMDA receptor activation, and recent studies have suggested that the subunit composition of these NMDA receptors (specifically whether the receptor complex contains the NR2A versus the NR2B subunit) plays an important role in whether their activation leads to LTP or LTD. However, these studies are primarily pharmacological, have provided conflicting results, and their conclusions remain somewhat controversial. The first aim of this proposal is to use pharmacological antagonists to determine whether the roles of the NR2A and NR2B in long-term plasticity change over development. The second aim is to investigate the roles of these subunits as molecular scaffolds in addition to their roles as receptor-channels. This will be done by evaluating the impact on LTP and LTD of decreasing NR2A and NR2B expression using RNAi. The third aim is to increase NR2A expression in the visual cortex of light-deprived rats to study the role of NR2A in experience-dependent plasticity.