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

NPAS4 对经验进行复杂的遗传编码，导致复杂的抑制重组。

基本信息

批准号：
10532239
负责人：
Daniel A Heinz
金额：
$ 4.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10532239
关键词：
Action Potentials Binding Biology Brain Calcium Channel Cell physiology Cells Cholecystokinin Complex Dendrites Environment Etiology Excitatory Postsynaptic Potentials Experimental Designs Exposure to FRAP1 gene Fire - disasters Gene Expression Gene Expression Regulation Genetic Genetic Identity Genetic Transcription Genome Hippocampus Human Inhibitory Synapse Interneurons Lead Link Location Mediating Messenger RNA Molecular Mus Myoepithelial cell NPAS4 gene Nervous System Physiology Neurologic Dysfunctions Neuronal Plasticity Neurons Organizational Change Pathway interactions Pattern Play Process Recurrence Regulation Role Slice Source Synapses Testing Transcript Translations Work cell type design environmental enrichment for laboratory animals experience experimental study hippocampal pyramidal neuron insight nervous system disorder neural neuronal cell body neuronal circuitry novel optogenetics postsynaptic programs response transcription factor voltage voltage clamp

项目摘要

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.

项目摘要当小鼠探索丰富的环境时，其海马 CA1 区域的锥体神经元接收兴奋性输入和火灾动作电位，以编码有关其复杂环境的信息。这经验诱导的活动导致活动依赖性转录因子 NPAS4 通过 de 表达 novo 转录和翻译，以及先前存在的 NPAS4 mRNA 的局部树突翻译。这富集环境诱导的 NPAS4 产生基因表达的变化，从而导致复杂的随着 CCK 篮子细胞数量的增加，体细胞树突轴上的抑制重组体细胞区域的突触和辐射树突上的抑制性突触数量减少 NPAS4 表达细胞。该提案描述了旨在确定 1) 遗传同一性的实验放射靶向中间神经元类型，其在 NPAS4 表达细胞上失去突触，以及 2) 在这种复杂的重组中，NPAS4 的树突翻译是必要的。这些实验将提供深入了解抑制网络复杂调节背后的基础生物学及其作用经验和活动依赖的树突翻译在此过程中发挥作用。鉴于已知的关系在抑制失调、树突翻译和各种神经系统疾病之间具有丰富的经验依赖症状学，这项工作将有助于我们理解神经功能和功能障碍。