Molecular mechanisms of infantile learning and memory

婴儿学习记忆的分子机制

• 批准号: 10684294
• 负责人: CRISTINA M ALBERINI
• 金额: $ 69.1万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 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/10684294
• 关键词: Address; Adult; Age; Animals; Behavior; Behavioral; Biological; Biological Process; Brain; Brain region; Cell Separation; Cells; Chronic; Cognition Disorders; Cognitive; Complex; Development; Dorsal; Episodic memory; Female; Functional disorder; Funding; Gene Expression; Genetic Transcription; Genetically Engineered Mouse; Hippocampus; 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 Profiling; Mus; Neurodevelopmental Disability; Neurodevelopmental Disorder; Neurons; 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; Visual; Work; base; behavioral study; cell type; cognitive ability; 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; member; memory process; memory recall; molecular imaging; novel; operation; prevent; response; sensory system; sex; social; spatial memory; trait; transcriptome; transcriptome sequencing; transcriptomics; translatome; virtual

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.

项目摘要 行为研究表明，早期生活经历显着塑造了大脑能力的发展。 因此，如果早期经历高度不平衡，例如如果它们在慢性的影响下发生 挑战或压力，个人的个性将发展特定的特征，包括 与严重的心理病理学有关。尽管有这些广泛的行为特征，但很少 关于早期学习和记忆的生物学机制已知，例外 创伤和压力的影响。了解学习和记忆的基础机制 早期开发是理解学习和记忆系统如何构建和 一生的功能，以及更好地阐明与神经发育相关的赤字 残疾。 大脑中最重要的系统之一是内侧颞叶依赖性内存 系统，该系统处理有关情节，空间，上下文和社会经验的信息。直到最近 人们认为，该记忆系统在婴儿期不起作用，因为它在发育中不成熟， 而且只有在开发后期才开始参与。但是，啮齿动物模型的最新研究，包括我们 自己，表明，情节和空间的学习形式需要生物学机制的功能 主区域的背侧海马（DHC）以及内侧的前额叶皮层（MPFC） 颞叶内存系统。尽管取得了最近的进展，但了解生物学和系统级的知识 缺乏婴儿，海马依赖性学习和记忆的机制。 为了填补这一知识差距，我们建议采用情节和空间学习的啮齿动物模型 工程鼠标模型，分子成像技术，空间转录组学和Ribotag鼠标 技术与OMIC分析相结合以追求以下特定目的：（1）映射分布 细胞网络的系统水平（DHC和MPFC），该细胞网络因婴儿期情节学习而激活 在记忆恢复中，在后来的提醒之后恢复，并测试恢复的锻造性和作用 成人行为的婴儿记忆。 （2）在原位DHC和MPFC基因表达上全面介绍 整个转录组的水平，并获得专门调节的综合翻译组 兴奋性和抑制性神经元，响应婴儿和成人大脑的学习。 这些实验将提供有关生物学和生物学和 系统级机制是婴儿学习和记忆的基础，以及无价的来源 关于神经发育和成人认知障碍的新假设的知识。