Fan cells in layer 2 of lateral entorhinal cortex are critical for episodic-like memory

Fan cells in layer 2 of lateral entorhinal cortex are critical for episodic-like memory
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外侧内嗅皮层第 2 层的扇细胞对于情景记忆至关重要

DOI:
10.1101/543777
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发表时间:
2019
期刊:
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影响因子:
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通讯作者:
Vandrey B
Vandrey B
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文献类型:
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作者:
Vandrey B

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情景记忆需要将不同类型的信息结合在一起,以产生对经历的表征。啮齿类动物的情景样记忆需要外侧内嗅皮层(LEC)和海马[1,2]。LEC对于整合物体的空间和上下文信息至关重要[2-6]。此外,LEC神经元对环境中的物体和物体之前经历过的位置进行编码,并在情节编码和检索过程中生成时间表征[7-12]。然而,目前尚不清楚LEC内的特定细胞群如何促进情景记忆成分的整合。LEC第2层(L2)在阿尔茨海默病(AD)及相关动物模型中表现出早期病理[13-16]。LEC的L2向海马的投射来自于浅表亚层(L2a)中的扇形细胞,这些细胞对reelin具有免疫反应,并投射到齿状回[17,18]。在这里,我们建立了一种使用Sim1:Cre小鼠选择性靶向风扇细胞的方法。尽管先前发现LEC的完全病变会破坏联想识别记忆[2,3],但我们报告说,在扇形细胞的突触输出选择性抑制后,小鼠可以区分新的物体-情境配置,但在识别新的物体-地点-情境关联方面受损。我们的研究结果表明,记忆功能在不同的LEC网络之间是分离的。
Episodic memory requires different types of information to be bound together to generate representations of experiences. The lateral entorhinal cortex (LEC) and hippocampus are required for episodic-like memory in rodents [1, 2]. The LEC is critical for integrating spatial and contextual information about objects [2–6]. Further, LEC neurons encode objects in the environment and the locations where objects were previously experienced and generate representations of time during the encoding and retrieval of episodes [7–12]. However, it remains unclear how specific populations of cells within the LEC contribute to the integration of episodic memory components. Layer 2 (L2) of LEC manifests early pathology in Alzheimer's disease (AD) and related animal models [13–16]. Projections to the hippocampus from L2 of LEC arise from fan cells in a superficial sub-layer (L2a) that are immunoreactive for reelin and project to the dentate gyrus [17, 18]. Here, we establish an approach for selectively targeting fan cells using Sim1:Cre mice. Whereas complete lesions of the LEC were previously found to abolish associative recognition memory [2, 3], we report that, after selective suppression of synaptic output from fan cells, mice can discriminate novel object-context configurations but are impaired in recognition of novel object-place-context associations. Our results suggest that memory functions are segregated between distinct LEC networks.