Rapid encoding of information alters the profile of plasticity related mRNA transcripts in the hippocampal CA3 region

A theoretical framework for the function of the medial temporal lobe system in memory defines differential contributions of the hippocampal subregions with regard to pattern recognition retrieval processes and encoding of new information. To investigate molecular programs of relevance, we designed a spatial learning protocol to engage a pattern separation function to encode new information. After background training, two groups of animals experienced the same new training in a novel environment, however only one group was provided spatial information and demonstrated spatial memory in a retention test. Global transcriptional analysis of the microdissected subregions of the hippocampus exposed a CA3 pattern that was sufficient to clearly segregate spatial learning animals from control. Individual gene and functional group analysis anchored these results to previous work in neural plasticity. From a multitude of expression changes, increases in camk2a, rasgrp1 and nlgn1 were confirmed by in situ hybridization. Furthermore, siRNA inhibition of nlgn1 within the CA3 subregion impaired spatial memory performance, pointing to mechanisms of synaptic remodeling as a basis for rapid encoding of new information in long-term memory. Keywords:behavioral intervention: spatial learning paradigm RNA samples from animals subjected to a spatial learning paradigm were compared to controls using Affymetirx RAE230a chips. An N of 7 was used in each of the two experimental conditions.

关于记忆中内侧颞叶系统（medial temporal lobe system）功能的理论框架，明确了海马亚区（hippocampal subregions）在模式识别提取过程与新信息编码方面的差异化贡献。为探究相关分子程序，我们设计了一项空间学习范式，以激活模式分离功能来完成新信息编码。在背景训练完成后，两组动物在全新环境中接受了相同的新训练，但仅其中一组被赋予空间信息，并在保持测验中表现出空间记忆能力。对显微切割获取的海马亚区进行全转录组分析后，我们发现海马CA3区的表达谱足以清晰区分空间学习组动物与对照组。单个基因与功能组分析将本研究结果与此前神经可塑性领域的相关研究进行了锚定关联。在大量表达变化的基因中，我们通过原位杂交技术验证了camk2a、rasgrp1及nlgn1的表达上调。此外，在海马CA3亚区中通过小干扰RNA（siRNA）抑制nlgn1的表达会损伤空间记忆能力，这表明突触重塑机制是长时记忆中快速编码新信息的基础。
关键词：行为干预，空间学习范式
本研究采用Affymetirx RAE230a基因芯片，对接受空间学习范式的动物的RNA样本与对照组样本进行了比较。两组实验条件下的样本量均为7。