Complex genetic encoding of experience by NPAS4 resulting in a sophisticated reorganization of inhibition.

项目摘要 当小鼠探索丰富的环境时，其海马区CA1区的锥体神经元 接收兴奋性输入和激发动作电位，以编码有关其复杂环境的信息。这 经验诱导的活性导致活性依赖的转录因子NPAS4通过De Novo转录和翻译，以及先前存在的NPAS4 mRNA的局部树突翻译。这 丰富的环境诱导NPAS4产生基因表达的变化，导致复杂的 横跨躯体-树突轴的抑制重组，CCK篮子细胞数量增加 体细胞区的突触和放射状树突上抑制性突触的数量减少 表达NPAS4的细胞。这份提案描述了用来确定1)基因同一性的实验 与NPAS4表达细胞失去突触的辐射靶向中间神经元型，以及2) 在这种复杂的重组中，NPAS4的树状结构翻译是必要的。这些实验将提供 洞察抑制网络复杂调控的基础生物学及其作用 依赖于经验和活动的树突翻译在这一过程中发挥了作用。考虑到已知的关系 抑制失调、树突状细胞转化和各种神经功能障碍之间的关系 依赖症状学，这项工作将有助于我们了解神经功能和功能障碍。

Project Abstract When a mouse explores an enriched environment the pyramidal neurons in the CA1 region of its hippocampus receive excitatory inputs and fire action potentials to encode information about their complex environment. This experience-induced activity results in the expression of the activity dependent transcription factor NPAS4 via de novo transcription and translation, as well as local dendritic translation of preexisting NPAS4 mRNA. This enriched environment induced NPAS4 produces changes in gene expression resulting in a sophisticated reorganization of inhibition across the somato-dendritic axis, with an increase in the number CCK Basket Cell synapses onto the somatic region and a decrease in the number of inhibitory synapses on the radiatum dendrites of NPAS4 expressing cells. This proposal describes experiments designed to determine 1) the genetic identity of the radiatum targeting interneuron type which loses synapses onto NPAS4 expressing cells, and 2) the necessity of dendritic translation of NPAS4 in this sophisticated reorganization. These experiments will provide insight into fundamental biology underlying the complex regulation of inhibitory networks and the role that experience and activity dependent dendritic translation play in this process. Given the known relationships between dysregulation of inhibition, dendritic translation, and a variety of neurological disorders with experience dependent symptomology, this work will aid our understanding of neurological function and dysfunction.