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

项目摘要/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。记忆有很强的空间性和 时间顺序分量。记忆研究领域长期以来一直使用啮齿动物的空间 线性环境中的导航作为研究记忆编码和 整合。对成年啮齿动物大脑进行了大规模电生理记录 在动物在新环境中航行的过程中已经建立了神经元集合 在海马体和内侧嗅觉皮质(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- 在进行任务时，海马体和mPFC神经元重新参与协调计算和 交流，特别是在成功的审判期间。内存和内存的最优研究 决策过程需要同时询问大量神经元集合 来自相互连接的大脑区域，如MEC和海马体，以及海马体和 MPFC。无一例外，这些实验都是在 在成年动物中，可以从行为自由的啮齿动物身上获得大的神经元样本。还没有 这些在成人大脑中的发现提出了新的关键问题，但仍未得到回答：何时以及如何 海马神经元群及其相互间的协调活动 上游/下游MEC在出生后出现，以支持编码和整合 关于长期记忆的？MPFC神经元集成模式何时以及如何对 决策的成熟以及它们与海马体的协调是如何在 出生后的生活？在这项建议中，我将调查年龄和经验依赖的早期- 已知对空间有重要意义的神经元集合模式的出生后发展 成年大鼠的记忆、导航和决策。长期的、大规模的 电生理记录将在几天内进行自由行为和 从相互连接的脑区同时睡眠发育中的和成年的大鼠，MEC和 分别是海马体和海马体和mPFC。这些实验将定义 大脑各连接区域协调发展的原则和阶段，其年龄 经验依赖和每个脑区特有的发育关键期 调查过了。

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.