Development and organization of brain-wide neuronal ensemble circuits underlying memory and decision making

记忆和决策的全脑神经元整体回路的开发和组织

• 批准号: 10671887
• 负责人: GEORGE DRAGOI
• 金额: $ 57.28万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2031-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671887
• 关键词: Adult; Age; Animals; Area; Brain; Chronic; Communication; Decision Making; Dependence; Development; Electrophysiology (science); Ensure; Environment; Episodic memory; Hippocampus; Investigation; Life; Medial; Memory; Neurons; Pattern; Process; Rattus; Research; Rodent; Sampling; Sleep; Therapeutic Intervention; cognitive function; critical developmental period; early onset; entorhinal cortex; executive function; experience; experimental study; long term memory; mature animal; memory consolidation; memory encoding; neuron development; neuropsychiatric disorder; novel; postnatal; postnatal development; preventive intervention; spatial memory; way finding

Project Summary/Abstract Episodic memory and memory-guided decision making are quintessential cognitive functions ensuring our identity, successful everyday life, and survival. Memories have a strong spatial and temporal sequential component. The field of memory research has long used rodent spatial navigation on linear environments as a framework for studying memory encoding and consolidation. Large-scale electrophysiological recordings from the adult rodent brain performed during animal navigation in novel environments have established that neuronal ensemble computations within and between the hippocampus and medial entorhinal cortex (MEC) are critical for the encoding and consolidation of spatial memories. During memory-guided decision- making tasks, the hippocampus and mPFC neurons re-engage in coordinated computations and communication, particularly during the successful trials. Optimal investigation of memory and decision-making processes require simultaneous interrogation of large ensembles of neurons from interconnected brain areas such as MEC and the hippocampus, and hippocampus and mPFC, respectively. Without exception, these experiments have been performed exclusively in adult animals where large neuronal samples could be obtained in freely-behaving rodents. Yet these findings in the adult brain raise new critical, still unanswered questions: When and how do coordinated activities between hippocampal neuronal ensembles and their upstream/downstream MEC emerge during postnatal life to support encoding and consolidation of long-term memories? When and how do mPFC neuronal ensemble patterns critical for decision making mature and how does their coordination with the hippocampus develop during postnatal life? In this proposal, I will investigate the age- and experience-dependent early- postnatal development of neuronal ensemble patterns known to be significant for spatial memory and navigation and decision making in the adult rat. The chronic, large-scale electrophysiological recordings will be performed over several days in freely-behaving and sleeping developing and adult rats simultaneously from interconnected brain areas, MEC and the hippocampus and the hippocampus and mPFC, respectively. These experiments will define the principles and stages of coordinated development across connected brain areas, their age and experience-dependence and the developmental critical periods specific to each brain area investigated.

项目总结/摘要 情景记忆和记忆引导的决策是典型的认知功能 确保我们的身份、成功的日常生活和生存。记忆具有很强的空间感和 时序分量记忆研究领域长期以来一直使用啮齿动物的空间 线性环境导航作为研究记忆编码的框架， 合并。成年啮齿动物大脑的大规模电生理记录 在动物在新环境中的导航过程中， 海马体和内侧内嗅皮层（MEC）内部和之间的计算是 对空间记忆的编码和巩固至关重要。在记忆引导的决策过程中- 在完成任务后，海马体和mPFC神经元重新参与协调计算， 特别是在试验成功的情况下。最佳的内存调查和 决策过程需要同时询问大量神经元 从相互连接的大脑区域，如MEC和海马，海马和 mPFC，分别。毫无例外，这些实验仅在 成年动物，其中大的神经元样本可以在自由行为的啮齿动物中获得。然而 这些在成人大脑中的发现提出了新的关键的，仍然没有答案的问题：什么时候以及如何 海马神经元群与其神经元之间的协调活动 上/下游MEC在出生后出现，以支持编码和巩固 长期记忆？mPFC神经元集合模式何时以及如何对 决策成熟，以及他们如何与海马协调发展， 产后生活？在这个建议中，我将调查年龄和经验依赖的早期- 出生后发育的神经元合奏模式已知是显着的空间 记忆、导航和决策的能力。慢性的，大规模的 电生理记录将在几天内进行自由行为， 睡眠发育和成年大鼠同时从相互连接的大脑区域，MEC和 海马体和海马体和mPFC。这些实验将定义 大脑各区域协调发展的原则和阶段， 和经验依赖性以及每个大脑区域特有的发展关键期 研究了