Differentiating between similar memories is a crucial cognitive function that enables correct episodic memory formation. The ability to separate the components of memories into distinct representations is thought to rely on a computational process known as pattern separation, by which differences are amplified to disambiguate similar events. Although pattern separation has been localized to the dentate gyrus (DG) of the hippocampus and shown to occur in a spatial domain, this cognitive function takes place also during processing of other types of information. In particular, there is some debate on whether the DG participates in pattern separation of nonspatial representations. Considering the classic role of the Prh in the acquisition and storage of object memories in general and tasks with similar features in particular, this cognitive function could rely more heavily on perirhinal regions when object‐related information is processed. Here we show that two plasticity‐related proteins, BDNF, and Arc, are required in the DG for nonspatial mnemonic differentiation. Moreover, we found that the crucial role of the DG is transient since activity of AMPAR is only required in the Prh but not the DG during differentiated object memory retrieval. Additionally, this memory is not modifiable by postacquisition rhBDNF infusions in the DG that are known to improve memory when given in the Prh. This highlights a differential role of Prh and DG during differentiated object memory consolidation. Additionally, we found that these molecular mechanisms actively interact in the DG and Prh for the formation of distinguishable memories, with infusions of rhBDNF in the Prh being able to rescue mnemonic deficits caused by reduced Arc expression in the DG. These results reveal a complex interaction between plasticity mechanisms in the Prh and DG for nonspatial pattern separation and posit the Prh as the key structure where unique object representations are stored.

中文翻译：

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齿状回和鼻周皮层内的分子机制在识别相似的非空间记忆时相互作用

区分相似的记忆是一个重要的认知功能，它能够正确地形成情景记忆。将记忆的组成部分分离成不同表示的能力被认为依赖于称为模式分离的计算过程，通过这种计算过程，差异被放大以消除相似事件的歧义。虽然模式分离已定位于海马的齿状回 (DG) 并显示发生在空间域中，但这种认知功能也发生在处理其他类型信息的过程中。特别是，关于 DG 是否参与非空间表示的模式分离存在一些争论。考虑到 Prh 在一般对象记忆的获取和存储以及具有相似特征的任务中的经典作用，当处理与对象相关的信息时，这种认知功能可能更多地依赖于鼻周区域。在这里，我们表明 DG 中需要两种与可塑性相关的蛋白质 BDNF 和 Arc 来进行非空间助记符分化。此外，我们发现 DG 的关键作用是短暂的，因为 AMPAR 的活动仅在 Prh 中需要，而在分化对象记忆检索期间 DG 不需要。此外，这种记忆不能通过 DG 中的获取后 rhBDNF 输注来修改，已知当在 Prh 中给予时可以改善记忆。这突出了 Prh 和 DG 在差异化对象记忆巩固过程中的不同作用。此外，我们发现这些分子机制在 DG 和 Prh 中积极相互作用以形成可区分的记忆，在 Prh 中注入 rhBDNF 能够挽救由 DG 中 Arc 表达减少引起的记忆缺陷。这些结果揭示了 Prh 和 DG 中用于非空间模式分离的可塑性机制之间的复杂相互作用，并将 Prh 作为存储唯一对象表示的关键结构。