DNA Recombination/Repair Mechanisms in Memory

记忆中的 DNA 重组/修复机制

基本信息

批准号：
7918871
负责人：
SANDRA PENA DE ORTIZ
金额：
$ 33.53万
依托单位：
UNIVERSITY OF PUERTO RICO RIO PIEDRAS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-24 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7918871
关键词：
Address Affect Amygdaloid structure Animals Behavioral Behavioral Paradigm Binding Biochemical Bioinformatics Biological Assay Brain Brain region Complement Control Groups DNA DNA Ligases DNA Microarray Chip DNA Restriction Enzymes DNA Sequence Rearrangement DNA ligase IV Data Down-Regulation Enzymes Epigenetic Process Event Flavoring Gene Expression Gene Expression Regulation Gene Rearrangement Gene Targeting Genes Genetic Recombination Genetic Transcription Genetic Variation Genome Genomics Hippocampus (Brain)Information Storage Infusion procedures Injection of therapeutic agent Laboratories Learning Ligase Longevity Lymphocyte Mediating Memory Metabolism Neurons Nonhomologous DNA End Joining Oligonucleotides Peptide Signal Sequences Play Polymerase Process Proteins RAG1 gene RTH-1 Nuclease Rattus Reaction Regulation Reporting Rodent Role Sampling Site Southern Blotting Specificity Structure Surgical Flaps Taste Perception Techniques Testing Time Training V(D)J Recombination Validation Visceral Work cDNA Probes caudate nucleus conditioned fear design endonuclease experience gene discovery inhibitor/antagonist laser capture microdissection long term memory recombinational repair research study response

项目摘要

DESCRIPTION (provided by applicant): Does the brain possess a mechanism for generating genetic diversity that could support memory storage? This proposal aims to test the idea that DNA recombination/repair mechanisms play a specific part in memory storage in the brain. Gene rearrangements may be used in the brain as a mechanism to generate experience-dependent protein diversity that could contribute to the storage of information acquired throughout a lifetime. DNA recombination may serve as a mechanism upstream of transcription to regulate the expression and function of a specific set of genes important for long-lasting memory storage. Thus, epigenetic, transcriptional, and recombinational mechanisms of gene regulation in memory do not exclude one another, but most likely complement each other. At this point, the most intriguing questions related to the idea of gene recombination and memory formation in the brain are what are the factors that mediate such a process in neurons and, more importantly, what are the genes that are subjected to this kind of regulation in response to learning. In this proposal, we focus on consolidation mechanisms of conditioned taste aversion (CTA), a behavioral paradigm characterized by the ability of many animals to learn to avoid certain substances after experiencing an unpleasant or harmful somatic (visceral) reaction. Aim # 1 of this proposal addresses the role of amygdalar DNA recombination mechanisms in consolidation of CTA in rats by using or gene knockdown approaches, both targeting the function of putative recombination effector enzymes, Flap Structure-Specific Endonuclease-1 (FEN-1) and DNA ligase IV. AIM # 2 examines amygdalar genomic rearrangement of putative DNA recombination target genes, such as protocadherin p9. Particularly, experiments will determine if the protocadherin 09 gene undergoes CTArelated genomic rearrangement in amygdala neurons. Overall, these studies will establish that DNA recombination/repair processes are part of the initial mechanisms utilized by the brain for the long-lasting storage of information, characterize the function of specific factors involved in this processes, and help demonstrate that specific gene targets undergo genomic rearrangement during memory formation.

描述（由申请人提供）：大脑是否具有产生可以支持记忆存储的遗传多样性的机制？该建议旨在测试DNA重组/修复机制在大脑中存储器中起特定角色的想法。基因重排可以在大脑中用作产生经验依赖性蛋白质多样性的机制，这可能有助于整个生命中获取的信息的存储。 DNA重组可以用作转录上游的一种机制，以调节一组对持久记忆存储重要的基因的表达和功能。因此，记忆中基因调控的表观遗传学，转录和重组机制并不排除彼此，但很可能相互补充。在这一点上，与大脑中基因重组和记忆形成的思想相关的最有趣的问题是介导神经元中这种过程的因素，更重要的是，哪些基因会响应学习而受到这种调节的基因。在此提案中，我们专注于条件味觉厌恶（CTA）的巩固机制，这是一种行为范式，其特征是许多动物在经历不愉快或有害的躯体（内脏）反应后学习避免某些物质的能力。该提案的目标＃1通过使用或基因敲低方法来解决大鼠CTA巩固CTA的作用，这既针并针对假定的重组效应酶的功能（瓣结构特定的内核酶-1（FEN-1）（FEN-1）（FEN-1）和DNA Ligase IV。 AIM＃2检查了推定的DNA重组靶基因，例如原粘蛋白P9的杏仁核基因组重排。特别是，实验将确定原钙粘蛋白09基因是否在杏仁核神经元中经历了基因组重排。总体而言，这些研究将确定DNA重组/修复过程是大脑用于持久信息存储的初始机制的一部分，表征了此过程中涉及的特定因素的功能，并有助于证明特定基因靶标在记忆形成过程中经历基因组重排。