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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：
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
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/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

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.

项目总结