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在加迷宫辨别性回避任务中依赖海马体的记忆:空间线索和CA1活性的作用。

Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.

作者信息

Leão Anderson H F F, Medeiros André M, Apolinário Gênedy K S, Cabral Alícia, Ribeiro Alessandra M, Barbosa Flávio F, Silva Regina H

机构信息

Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.

Laboratory of Behavioral Neuroscience, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

出版信息

Behav Brain Res. 2016 May 1;304:24-33. doi: 10.1016/j.bbr.2016.02.012. Epub 2016 Feb 10.

Abstract

The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 μg, 0.1 μg, and 0.2 μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to elucidate how these memory systems interact during aversive memory formation. Thus, the PMDAT can be useful for studying hippocampal-dependent memory when it involves emotional content.

摘要

加迷宫辨别性回避任务(PMDAT)已被用于研究啮齿动物中厌恶记忆与焦虑样反应之间的相互作用。与其他基于厌恶的记忆任务类似,该任务的良好表现取决于基底外侧杏仁核的活动。然而,空间线索和海马依赖性学习在PMDAT表现中的作用仍不清楚。在此,我们研究了近端和远端线索在该任务检索中的作用。在近端线索位置错误的情况下进行测试的动物表现下降,而在近端线索位置错误且远端线索缺失的情况下进行测试的动物无法辨别厌恶臂。我们还评估了背侧海马体(CA1)在这个厌恶记忆任务中的作用。在训练前用蝇蕈醇(0.05μg、0.1μg和0.2μg)对背侧CA1进行短暂双侧失活。虽然任务的习得没有改变,但蝇蕈醇损害了测试环节的表现,并降低了训练环节中的焦虑样反应。我们还对荧光团偶联的蝇蕈醇进行了扩散分析,以确认对CA1的选择性抑制。总之,检索该任务既需要远端线索也需要近端线索,后者与空间定向更相关。背侧CA1的活动在该任务的厌恶记忆形成中也是必需的,并且也干扰了焦虑样反应。重要的是,在同一范式中通过不同参数检测到了这两种效应,支持了之前在PMDAT中对厌恶记忆和焦虑样行为进行独立评估的发现。综上所述,这些发现表明PMDAT可能需要多个系统整合来形成记忆,类似于情景样记忆而非单纯的条件行为。此外,在啮齿动物中对情绪和记忆进行同时且独立的评估,对于阐明这些记忆系统在厌恶记忆形成过程中如何相互作用是有意义的。因此,当涉及情绪内容时,PMDAT可用于研究海马依赖性记忆。

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