Molecular mechanisms of infantile learning and memory

婴儿学习记忆的分子机制

基本信息

批准号：
10297488
负责人：
CRISTINA M ALBERINI
金额：
$ 67.25万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-10 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297488
关键词：
Address Adult Age Animals Behavior Behavioral Biological Biological Process Brain Brain region Cells Chronic Cognition Disorders Cognitive Complex Development Dorsal Episodic memory Female Functional disorder Funding Gene Expression Genetic Transcription Genetically Engineered Mouse Hippocampus (Brain)Hour Imaging technology Immediate-Early Genes Immunohistochemistry In Situ Individual Infant Investigation Knowledge Learning Life Life Experience Link Maps Medial Memory Mental Health Messenger RNA Molecular Molecular Genetics Molecular Profiling Mus Neurodevelopmental Disability Neurodevelopmental Disorder Neurons Operating System Pathway interactions Personality Prefrontal Cortex Process Psychopathology Rattus Recovery RiboTag Ribosomes Rodent Model Role Shapes Source Stains Stimulus Stress System Technology Temporal Lobe Testing Time Transcript Translating Trauma Work base behavioral study biological systems cell type cognitive ability cognitive development critical developmental period critical period designer receptors exclusively activated by designer drugs early experience excitatory neuron experience experimental study genetic technology infancy infant animal inhibitory neuron interest male memory process memory recall molecular imaging novel operation prevent response sensory system sex social spatial memory trait transcriptome transcriptome sequencing transcriptomics translatome virtual

项目摘要

Project Summary Behavioral studies have shown that early life experience significantly shapes the development of brain abilities. Accordingly, if early experiences are highly unbalanced, e.g. if they occur under the influence of chronic challenges or stresses, the individual's personality will develop specific traits, including some that are associated with severe psychopathologies. Despite these extensive behavioral characterizations, very little is known about the biological mechanisms underlying learning and memory in early life, with the exception of the effects of trauma and stress. Understanding the mechanisms underlying learning and memory in early development is key for comprehending how the learning and memory systems are built and function throughout life, as well as to better elucidate the deficits associated to neurodevelopmental disabilities. One of the most important systems operating in the brain is the medial temporal lobe-dependent memory system, which processes information about episodic, spatial, contextual and social experiences. Until recently it was believed that this memory system does not function in infancy because it is developmentally immature, and only begins to be involved late in development. However, recent studies in rodent models, including our own, showed that episodic and spatial forms of learning require the function of biological mechanisms in the dorsal hippocampus (dHC), a main region, together with the medial prefrontal cortex (mPFC), of the medial temporal lobe memory system. Despite this recent progress, knowledge of the biological and system-level mechanisms of infantile, hippocampus-dependent learning and memory is lacking. To fill this knowledge gap we propose to employ rodent models of episodic and spatial learning, genetically engineered mouse models, molecular imaging technology, spatial transcriptomics and RiboTag mouse technology combined with omic analyses to pursue the following specific aims: (1) To map the distribution at a system level (dHC and mPFC) of the cellular networks activated in response to episodic learning in infancy and in memory recovery following reminders at later ages, and to test the malleability and roles of recovered infantile memories in adult behavior. (2) To comprehensively profile in situ dHC and mPFC gene expression at the level of the whole transcriptome, as well as obtain a comprehensive translatome specifically regulated in excitatory and inhibitory neurons, in response to learning in both infant and adult brains. These experiments will provide an unprecedented amount of novel information regarding the biological and system-level mechanisms underlying infantile learning and memory, as well as an invaluable source of knowledge for generating novel hypotheses regarding neurodevelopmental and adult cognitive disorders.

项目概要行为研究表明，早期生活经历显着影响大脑能力的发展。因此，如果早期经历高度不平衡，例如如果它们发生在慢性病的影响下当面临挑战或压力时，个人的性格会发展出特定的特征，包括一些与严重的精神病理学有关。尽管有这些广泛的行为特征，但很少有了解早期生活中学习和记忆的生物机制，但例外创伤和压力的影响。了解学习和记忆的潜在机制早期发展是理解学习和记忆系统如何构建的关键终生功能，以及更好地阐明与神经发育相关的缺陷残疾。大脑中最重要的系统之一是内侧颞叶依赖性记忆系统，处理有关情景、空间、情境和社会体验的信息。直到最近人们认为这种记忆系统在婴儿期不起作用，因为它发育不成熟，并且直到后期才开始参与开发。然而，最近对啮齿动物模型的研究，包括我们的自己的研究表明，情景和空间形式的学习需要生物机制的功能背侧海马 (dHC) 是内侧前额皮质 (mPFC) 的一个主要区域颞叶记忆系统。尽管最近取得了进展，但生物和系统层面的知识缺乏婴儿期依赖海马体的学习和记忆机制。为了填补这一知识空白，我们建议采用情景和空间学习的啮齿动物模型，从遗传上讲工程小鼠模型、分子成像技术、空间转录组学和 RiboTag 小鼠技术与组学分析相结合，以实现以下具体目标：（1）绘制分布图响应婴儿期情景学习而激活的细胞网络的系统级（dHC 和 mPFC）并在晚年提醒后进行记忆恢复，并测试恢复后的可塑性和作用成人行为中的婴儿记忆。 (2) 全面分析 dHC 和 mPFC 基因在整个转录组的水平，以及获得一个全面的翻译组，特别是在兴奋性和抑制性神经元，对婴儿和成人大脑的学习做出反应。这些实验将提供前所未有的大量关于生物和婴儿学习和记忆的系统级机制，以及宝贵的资源生成有关神经发育和成人认知障碍的新假设的知识。