Contributions of Hippocampal Subsystems to Different Aspects of Episodic Memory

人们习惯性地将复杂的日常环境中的经验流组织成片段，这些片段最少包含关于发生了什么、不同物品或事件的位置以及它们发生的顺序的信息。海马体在大脑形成这些情景记忆的过程中起着至关重要的作用。研究人员和其他人的研究发现，啮齿动物获得了简化版本的“什么”，“哪里”和“何时”记忆;随后的神经行为研究确定了与这些记忆相关的海马网络。拟议的实验将确定动物是否也表达人类情景记忆的另外两个关键特征-使用上下文检索特定情节和一个项目来提示回忆下一个-然后定位底层网络。初步结果表明，啮齿动物利用这两种操作。描述这些功能背后的网络级操作将使工作情景记忆的贡献，高阶认知操作，包括推理思维，这是至关重要的人类经验。它还可以指出计算机化学习系统的方向，克服现有人工智能版本的已知限制。拟议的工作将使用申请人实验室开发的啮齿动物学习范例的修改形式。这些涉及到气味的序列，这些线索是动物天生的兴趣。该协议不需要重复或公开的奖励，因此与人类情景记忆的主要方面保持一致。这项工作的网络追踪部分将采用化学遗传学技术来暂时沉默海马和相关结构内的特定通路。将根据一般假设和相关计算机模型对结果进行评估。除了科学进步，该项目还将为高中生、本科生和研究生提供培训、指导和研究活动的环境。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

People routinely organize the flow of experience in complex everyday environments into episodes that minimally contain information about what happened, where different items or events were located, and the order in which they occurred. The hippocampus plays a critical role in the brain’s formation of these episodic memories. Studies by the investigator and others found that rodents acquire simplified versions of ‘what’, ‘where’, and ‘when’ memory; subsequent neurobehavioral investigations identified hippocampal networks associated with each of these. The proposed experiments will determine if the animals also express two other critical features of human episodic memory – using context to retrieve a specific episode and one item to prompt recall of the next -- and then localize the underlying networks. Preliminary results suggest that rodents utilize both of these operations. A description of the network level operations underlying these functions would enable work on episodic memory’s contributions to higher order cognitive operations, including inferential thinking, that are vital to the human experience. It could also point the way to computerized learning systems that obviate known limitations on present versions of artificial intelligence.The proposed work will use modified forms of rodent learning paradigms developed in the applicant’s laboratory. These involve sequences of odors, cues that are of innate interest to the animals. The protocols do not require repetition or overt rewards and thus align with cardinal aspects of human episodic memory. The network-tracing portion of the work will employ chemogenetic techniques for transiently silencing specific pathways within the hippocampus and allied structures. Results will be evaluated with regard to a general hypothesis and associated computer models. In addition to the scientific advances, the project will provide an environment of training, mentoring and research activities for high school, undergraduate and graduate students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.