Pattern Separation and Generalization in the Hippocampus

描述(由申请人提供)：尽管已经出现了大量令人印象深刻的证据支持海马体在陈述性记忆中的基本作用，但海马体内单个结构对记忆的贡献方式仍然是当前争论的主题。这项建议的中心目标是评估海马亚区之间的回路差异如何转化为支持情景记忆形成的功能差异。在形成新的记忆时，海马体被认为将相关的输入模式分离成不同的表征，从而将相似记忆痕迹之间的干扰降至最低。然而，来自神经网络模型和动物研究的发现表明，海马体内存在紧张，因此一些子场容易促成模式分离，而另一些子场则倾向于概括类似的输入模式。使用高分辨率功能磁共振成像(FMRI)，这项拟议的研究旨在评估人类海马子场在多大程度上支持在项目和项目间水平上的相似性操作下形成非重叠和共享的记忆表征。此外，为了补充这种高空间分辨率的fMRI方法，将直接从人类海马区记录局部场电位，以更好地表征模式分离和泛化的时间分布。描绘海马区调节记忆的方式将推进对海马体功能的机械解释，并提供对具有模式分离缺陷的人群(如老年人和精神分裂症患者)受影响的大脑区域的洞察。 与公共健康相关：描绘海马区调节记忆的方式将推进对海马区功能的机械性描述，并增加对人类大脑中如何形成不同的记忆表征的理解。反过来，这些发现可能会成为研究人员检查海马体解剖和功能变化的基础，这些人在形成独特记忆方面存在缺陷，比如老年人和精神分裂症患者。

DESCRIPTION (provided by applicant): Although an impressive amount of evidence has emerged supporting a fundamental role for the hippocampus in declarative memory, the manner in which individual structures within the hippocampus contribute to memory remains a current topic of debate. The central objective of this proposal is to evaluate how differences in circuitry among hippocampal subfields translate to functional differences in support of episodic memory formation. In forming new memories, the hippocampus is thought to separate related input patterns into distinct representations, thereby minimizing interference between similar memory traces. However, findings from neural-network models and animal studies suggest that tension exists within the hippocampus such that some subfields readily contribute to pattern separation, whereas others tend to generalize across similar input patterns. Using high-resolution functional magnetic resonance imaging (fMRI), the proposed research aims to evaluate the degree to which human hippocampal subfields support the formation of non-overlapping vs. shared memory representations in response to similarity manipulations at both the item and inter-item level. Furthermore, to complement this high spatial resolution fMRI approach, local field potentials will be directly recorded from the human hippocampus to better characterize the temporal profile of pattern separation and generalization. Delineating the manner in which hippocampal subfields mediate memory will advance mechanistic accounts of hippocampal function, as well as provide insights into brain regions affected in populations exhibiting pattern separation deficits, such as older adults and individuals with schizophrenia. PUBLIC HEALTH RELEVANCE: Delineating the manner in which hippocampal subfields mediate memory will advance mechanistic accounts of hippocampal function and increase understanding of how distinct memory representations are formed in the human brain. In turn, such findings may serve as a foundation from which researchers can examine anatomical and functional changes in the hippocampus in populations exhibiting deficits in forming distinct memories, such as older adults and individuals with schizophrenia.