Dynamic modulation of postnatal development of preconfigured and plastic time-compressed sequences

预配置和可塑时间压缩序列的出生后发育的动态调节

• 批准号: 10672466
• 负责人: GEORGE DRAGOI
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10672466
• 关键词: Acceleration; Address; Adult; Affect; Age; Amnesia; Animals; Area; Behavioral; Binding; Birth; Brain; Brain Diseases; Cells; Characteristics; Chronic; Code; Complex; Computing Methodologies; Dependence; Deterioration; Development; Electrophysiology (science); Enhancers; Episodic memory; Event; Eye; Goals; Hippocampus; Home; Human; Infusion procedures; Intellectual functioning disability; Life; Life Experience; Location; Memory; Nerve Growth Factors; Neurons; Pattern; Play; Process; Psyche structure; Rattus; Reporting; Rest; Rodent; Role; Schizophrenia; Sleep; Synaptic plasticity; System; Therapeutic Intervention; Time; Visual; age related; autism spectrum disorder; awake; cognitive function; critical developmental period; dark rearing; early onset; environmental enrichment for laboratory animals; experience; forgetting; infancy; member; memory consolidation; memory encoding; neural; neuropsychiatric disorder; neuropsychiatry; novel; postnatal; postnatal development; preservation; preventive intervention; programs; visual deprivation

Project summary: Of the multiple memory systems operating in the brain, episodic memory, defined by the ability to remember where and when events occurred in the past, is a recently evolved, later developing and early deteriorating cognitive function. Early-life episodic memories are rapidly forgotten, a phenomenon known as infantile amnesia occurring in humans and non-human animals. The hippocampus, an evolutionarily ancient, highly organized part of the cortex, is essential for the relational binding of spatial locations and events into spatial and mental trajectories and memory episodes. The rapid encoding and consolidation of sequential spatial experiences into memory episodes is believed to be achieved by the representation of such trajectories within time-compressed hippocampal ‘place cell’ sequences during navigation and the sleep/rest periods preceding (i.e., preplay, supporting rapid encoding) and following (i.e., replay, supporting consolidation) the novel experiences. The hippocampus undergoes a developmental critical period and functionally matures around postnatal day 24 (P24) in the rat, an age when infantile amnesia ends in rodents. Our main goal is to explore and understand the dependence of memory development on intrahippocampal synaptic plasticity and early-life experience by studying the development of ensemble place cell coding in the hippocampus. We combine chronic electrophysiologic recording of large ensembles of neurons in awake-behaving and sleeping rats across three recently described developmental stages in postnatal life with intra-hippocampal infusion of enhancers of synaptic plasticity, rearing in enriched environments or early-life visual deprivation (dark rearing), and computational methods for decoding spatial trajectories. The successful completion of our proposed aims promises to uncover such developmental mechanism and factors in the rat, which should help understand the development and emergence of episodic memories in the human, where such invasive approaches are not possible. Our findings could more generally impact our understanding of developmental neuro-psychiatric brain diseases like autism, schizophrenia, and intellectual disabilities.

项目总结：在大脑中运作的多个记忆系统中，情景记忆由