Distributed synaptic plasticity in fear conditioning

描述（由申请人提供）：大鼠中的巴甫洛夫恐惧条件反射是目前用于在分子、细胞和系统水平上研究记忆的强有力的模型系统。最近的研究表明，恐惧条件反射的长期记忆的形成需要杏仁核和海马体中新的mRNA和蛋白质的合成。此外，似乎这些记忆从存储中恢复后，它们会经历第二个时间段，在此期间需要蛋白质合成。我们的数据表明，虽然最初的学习需要在杏仁核神经元的mRNA和蛋白质的合成，“稳定”的记忆后检索不需要mRNA转录。这表明，虽然最初的记忆形成需要核转录，但提取后突触的修饰可能涉及使用局部mRNA的树突蛋白质合成。我们还提供了证据表明，mRNA和/或蛋白质的合成所需的新的学习不仅在杏仁核，而且在整个神经回路的结构在恐惧条件反射活跃。 本文提出的实验将评估mRNA转录和蛋白质翻译对多个大脑部位记忆巩固和“再巩固”的相对贡献，这些大脑部位包括杏仁核、海马、丘脑内侧膝状体核和中脑导水管周围灰质区。我们将在几个地点描述这些过程的相对训练后时间过程，并开始探索每个大脑区域对学习的特定功能贡献。 这些结果将为记忆形成机制和分子和系统水平的长期稳定性提供重要的新见解。

.DESCRIPTION (provided by applicant): Pavlovian fear conditioning in rats is a powerful model system currently being used to study memory at the molecular, cellular, and systems level. Recent work with this procedure indicates that the formation of long-term memory for fear conditioning requires the synthesis of new mRNA and protein in the amygdala and hippocampus. Furthermore, it appears that after these memories are retrieved from storage they go through a second time period during which protein synthesis is required. Our data indicate that while initial learning requires both mRNA and protein synthesis in amygdala neurons, the "stabilization" of memory after retrieval does not require mRNA transcription. This suggests that while initial memory formation requires nuclear transcription, the modification of synapses after retrieval may involve dendridic protein synthesis using local mRNA. We also provide evidence showing that mRNA and/or protein synthesis is required for new learning not only in the amygdala, but also in structures throughout the neural circuit active during fear conditioning. The experiments proposed here will evaluate the relative contribution of mRNA transcription and protein translation to memory consolidation and "reconsolidation" at multiple brain sites including the amygdala, hippocampus, medial geniculate nucleus of the thalamus, and periaqueductal gray region of the midbrain. We will describe the relative post-training time course of these processes at several sites and begin to explore specific functional contributions of each brain area to learning. The results will provide important new insights into the mechanisms of memory formation and long-term stability at the molecular and systems level.