Hippocampal IncRNAs and Memory Consolidation

海马 IncRNA 和记忆巩固

基本信息

批准号：
9341208
负责人：
Sathyanarayanan V Puthanveettil
金额：
$ 24万
依托单位：
SCRIPPS FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9341208
关键词：
Animals Behavioral Behavioral Assay Cell Nucleus Characteristics Cognition Disorders Communication Cytoplasm Data Dementia Development Disease Drug Addiction Epigenetic Process Gene Expression Gene Expression Profile Gene Expression Regulation Genetic Transcription Genetic Translation Genome Goals Hippocampus (Brain)In Situ Hybridization Large-Scale Sequencing Learning Mediating Memory Mental disorders Messenger RNA Modification Molecular Mus Nervous system structure Neurons Neurosciences Nucleotides Outcome Pharmacology Population Post-Traumatic Stress Disorders Prefrontal Cortex Regulation Research Research Personnel Resources Role Testing Therapeutic Therapeutic Intervention Time Training Transcript Translations Untranslated RNA addiction base conditioned fear dentate gyrus design differential expression epigenetic regulation experience experimental study fear memory innovation insight knock-down long term memory mRNA Stability memory consolidation memory encoding neural circuit novel novel therapeutics public health relevance success therapeutic candidate transcriptome

项目摘要

DESCRIPTION (provided by applicant): Developing successful treatments for cognitive disorders such as dementia is a major goal in neuroscience. Key to the development of novel therapeutics for cognitive disorders is the understanding of the molecular and cellular basis of how memories are encoded, maintained and eventually erased. Here we propose to study the contribution of a novel class of candidates, long-noncoding RNAs (lncRNAs), to contextual fear memory, a form of associative memory in which an animal forms strong association of a fearful experience to a context. Because of the potential roles of lncRNAs as regulators of transcription and translation, elucidating lncRNA function in neuronal communication and long-term memory (LTM) storage will facilitate identification of novel targets for developing therapeutics for cognitive disorders. The central hypothesis of this proposal, based on our own preliminary data, is that specific changes in the expression of lncRNAs in the hippocampus mediate the consolidation of contextual fear memories. To test this hypothesis, we will use the contextual fear-conditioning (CFC) paradigm that produces long-lasting fear memories in mice as a behavioral assay and then determine whether expression of specific lncRNAs in CA1, CA3 and dentate gyrus (DG) neurons of the hippocampus are critical for the consolidation of contextual fear memories. An anticipated outcome of this proposed research is that once the specific lncRNAs that are regulated during contextual fear memory storage are identified, they may be manipulated pharmacologically, producing new and innovative approaches to the treatment of disorders such as post-traumatic disorders.

描述（由适用提供）：为痴呆等认知障碍开发成功治疗是神经科学的主要目标。开发新的认知疾病疗法的关键是对记忆如何编码，维护和最终消除的分子和细胞基础的理解。在这里，我们建议研究一类新型候选人，长期非编码RNA（LNCRNA）对上下文恐惧记忆的贡献，这是一种联想记忆的一种形式，在这种形式上，动物在上下文中形成了恐惧体验的牢固关联。由于LNCRNA作为转录和翻译的调节剂的潜在作用，阐明LNCRNA功能在神经元通信和长期记忆（LTM）存储中的作用将有助于鉴定出用于开发认知障碍治疗的新目标。该提案的核心假设是基于我们自己的初步数据，是在海马中位数中LNCRNA表达的特定变化是情境恐惧记忆的巩固。为了检验这一假设，我们将使用上下文恐惧调节（CFC）范式，该范式在小鼠中产生持久的恐惧记忆作为行为评估，然后确定在CA1，CA3，CA3和齿状回和齿状回（DG）神经元中是否表达了河马的神经元的河马神经元的融合对情境恐惧的构造至关重要。这项拟议的研究的预期结果是，一旦确定了情境恐惧记忆存储期间受调节的特定LNCRNA，就可以通过药物进行操纵，从而产生新的和创新的方法来治疗诸如创伤后疾病之类的疾病。