Nonspecific ensemble reactivation in mouse dentate gyrus disrupts spatial working memory

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-15 DOI:10.1016/j.isci.2025.113566

Lucius K. Wilmerding , Ivan Kondratyev , Wen Bing Shi , Steve Ramirez , Michael E. Hasselmo

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Abstract

Spatial working memory enables behavioral flexibility and depends upon the hippocampus. The hippocampal dentate gyrus (DG) is hypothesized to act as a pattern separator to disambiguate similar memories. We used activity-dependent labeling strategies in DG to tag multiple memory-associated neuronal ensembles recruited during the course of learning a spatial working memory task. We termed the tagged ensembles “nonspecific” because they arose from experiences across days, maze arenas, and the home cage. Optogenetic stimulation of nonspecific ensembles during the encoding phase within random trials of the task acutely impaired performance during light-on trials only. The degree of reactivation in the dentate hilus, but not the blade, inversely correlated with task accuracy. While our results do not rule out the possibility that the stimulation of random, sparse DG ensembles could lead to similar impairment, they are consistent with the proposed role of DG in pattern separation, completion, and spatial working memory.

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小鼠齿状回非特异性集合再激活破坏空间工作记忆

空间工作记忆使行为具有灵活性，并取决于海马体。海马体齿状回（DG）被假设为一种模式分离器来消除相似记忆的歧义。我们在DG中使用活动依赖标记策略来标记在学习空间工作记忆任务过程中招募的多个记忆相关神经元群。我们将标记的集合称为“非特异性”，因为它们来自于白天、迷宫竞技场和家庭笼子的经历。在随机试验中，仅在光照试验中，在编码阶段对非特异性集合进行光遗传刺激会严重损害任务的表现。齿状门的再激活程度与任务的准确性呈负相关，而不是刀刃。虽然我们的研究结果不排除随机、稀疏的DG集合刺激可能导致类似损伤的可能性，但它们与DG在模式分离、完成和空间工作记忆中的作用是一致的。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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