灵长类动物内侧颞叶中语义记忆与情景记忆间的交互作用对行动的作用

Declarative memory makes it possible for us to remember the past and to make appropriate choices based on our past experiences. This everyday-language memory consists of two subcategories: semantic memory and episodic memory. The former refers to general knowledge of facts, while the latter refers to memories of autobiographical events containing item, time and place. Many studies including both human and animal experiments investigated these two memory functions. However, only few studies examined interactions between them. In this proposal, we will examine their interactions at single-neuron level particularly when we use our knowledge for the future action. For this aim, we have devised a novel memory task for monkey neurophysiology. We refer to this task as a prospective brain for monkey (PBM) task, concerned with "prospective brain" paradigm which is proposed by recent human fMRI studies. In the PBM task, a monkey retrieves a long-term association memory between item and place, and then the animal uses the to-be-retrieved information for the action in a flexible manner according to a following instruction cue. We assume that the item-place associations will be stored as semantic-like memory rather than episodic-like memory because monkey subjects will learn the combinations repeatedly over one year of the training period. We will record single-unit activities and local field potentials from the medial temporal lobe (MTL), visual area TE (TE) and the retrosplenial cortex (RSC) during the monkeys are performing the task. MTL is a center of declarative memory system and consists of the hippocampus, the entorhinal cortex, the perirhinal cortex and the parahippocampal cortex. Anatomically, TE provides object information to MTL, while RSC provides spatial information to MTL. In this project, we will ask two main questions as follows. The first question is which brain area stores the association between item and place as long-term memory; is it the perirhinal cortex or the hippocampus? The second question is how MTL areas and RSC use the to-be-retrieved information for the future action; what kind of neural mechanisms are recruited in MTL and RSC to transform the place information from an allocentric cognitive map to an egocentric spatial map? The answers to these questions will provide the first neurophysiological evidence indicating the manipulation of to-be-stored semantic information by episodic memory system.

陈述性记忆由语义记忆和情景记忆组成，前者指一般的知识、概念，后者是包含了事件及其发生时间、地点等的自传式回忆。多数研究集中于阐明这两种记忆各自的功能特征，其相互关系并不清楚。本研究将基于我们运用自身知识对未来事件做出决策这一现象，在单细胞水平上探究这种相互关系。我们设计了一个前瞻性脑力（PBM）任务，其中猕猴被训练记住若干组物体－方位配对关联，通过检索记忆信息完成配对任务。因为反复学习，这种关联最终被储存为类语义记忆。记录猕猴任务时其内侧颞叶（MTL），视觉皮层TE和压后皮质（RSC）等区域的单细胞和局部场电位活动。MTL是陈述性记忆系统的中心，TE、RSC分别向MTL输入物体、方位信息。我们试图回答：第一，哪部分脑区储存了这种物体－方位关联的长期记忆？第二，MTL和RSC如何运用待检索记忆支持未来抉择？找到第一步的情景记忆系统运用语义记忆信息支持未来决策的神经电生理依据。

近年来，fMRI领域发表了越来越多与 “前瞻性脑力”相关的研究。但是，在动物生理学领域却几乎未发表相关的研究。我们设计了新颖的适用于猕猴的“前瞻性脑力”（PBM）实验范式，目前已成功解决了我们在本研究计划中提出的两大问题。在该实验范式中，我们训练猕猴使其记住8个物体在一个大型背景上的相对位置。在每一次实验试次中，其中一个物体会作为物体线索呈现，随后，背景图以随机角度呈现以作为方位线索。根据该试次中出现的物体及背景的角度，猕猴需要扫视到目标位置。我们在猕猴执行PBM任务时总共记录了1374个神经元，这些神经元所覆盖的脑区包括内侧颞叶（MTL）中的海马区（HPC）、海马旁回（PHC）、内嗅皮质（ERC）和外嗅皮质（PRC），以及TE区和7a区。通过统计分析，我们发现大量任务相关的神经元。其中一类是物体线索选择性神经元。在这一类神经元中，除了TE区的神经元之外，其他区域的神经元都对关联于相同相对位置的两个同组物体具有相似的选择性。我们将这些对同组物体具有显著正相关反应的神经元称为“同位（co-locating）神经元”。随后，我们比较了不同脑区中同位神经元对同组物体反应相关系数的时间过程，其中，PRC比HPC较早呈现显著正相关，PHC和7a则较晚呈现。该结果表明，物体-方位关联信息可能作为类语义记忆形式存储于PRC中（回答了问题一）。我们进一步对方位线索呈现之后的时间段进行统计分析，发现了对物体线索或方位线索具有选择性的神经元。在我们所记录的区域中，HPC具有最高比例的此类神经元，尤其是对物体线索和方位线索同时具有选择性或具有交互作用的神经元。该结果暗示了物体与方位信息的整合可能发生于HPC。进一步分析表明，HPC将所提取的物体关联位置信息按步骤转化为目标位置。这些结果表明，将所提取的语义记忆与当前空间背景进行整合的过程发生于HPC（回答了问题二）。综上所述，该研究首次证明了记忆信息的关联进程源于皮层HPC，并为情景记忆中的“建设性理论（constructive theory）”提供了进一步的证据。

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