Novel Object Recognition in Rats With NMDAR Dysfunction in CA1 After Stereotactic Injection of Anti-NMDAR Encephalitis Cerebrospinal Fluid
Novel Object Recognition in Rats With NMDAR Dysfunction in CA1 After Stereotactic Injection of Anti-NMDAR Encephalitis Cerebrospinal Fluid
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DOI：
10.3389/fneur.2019.00586
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发表时间：
2019-06-05
影响因子：
3.4
通讯作者：
Kirschstein, Timo
中科院分区：
文献类型：
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作者：
Kersten, Maxi;Rabbe, Theresa;Kirschstein, Timo
目的：与n -甲基d -天冬氨酸受体（NMDARs）自身抗体相关的边缘脑炎通常表现为记忆障碍。NMDARs是记忆获取和检索的关键靶点，并与其潜在的过程突触可塑性有机制联系。在临床上，记忆缺陷在很大程度上与主要依赖海马体的表型相一致，在啮齿动物中，这种表型主要涉及空间记忆。以往的研究证实了抗nmdar脑炎大鼠模型的空间记忆受损。在这里，我们假设非空间记忆功能，如物体识别也可能在这个模型中受到影响。方法：将抗nmdar脑炎和对照组的脑脊液立体定向注入麻醉大鼠海马内。恢复1-8天后，从这些动物身上制备海马切片，并在Schaffer侧侧- ca1突触评估nmda依赖的长期增强。此外，我们使用开放场和新目标识别任务进行了行为分析。结果：海马CA1区NMDAR依赖性长时程增强被显著抑制，表明该亚区NMDAR功能障碍成功。自然运动活动和焦虑相关行为在nmdar - csf治疗的动物和对照动物之间没有差异。在新的目标识别任务中，两组在接近目标的动机上没有差异。相比之下，我们观察到只有在对照组中有明显的偏好探索新物体，而在nmdar - csf治疗的大鼠中没有。结论：海马内立体定向注射导致的NMDAR功能障碍不会改变运动或焦虑相关行为。此外，对物体的接近或一般的探索行为也不受影响，但完整的初始nmdar依赖过程可能涉及新物体识别。
Purpose: Limbic encephalitis associated with autoantibodies against N-methyl D-aspartate receptors (NMDARs) often presents with memory impairment. NMDARs are key targets for memory acquisition and retrieval, and have been mechanistically linked to its underlying process, synaptic plasticity. Clinically, memory deficits are largely compatible with a pre-dominantly hippocampus-dependent phenotype, which, in rodents, is principally involved in spatial memory. Previous studies confirmed the impaired spatial memory in the rat model of anti-NMDAR encephalitis. Here, we hypothesized that non-spatial memory functions, such as object recognition might also be affected in this model.Methods: We performed stereotactic intrahippocampal bolus injection of human cerebrospinal fluid (CSF) from anti-NMDAR encephalitis and control patients into the hippocampus of the anesthetized rat. After recovery for 1-8 days, hippocampal slices were prepared from these animals and NMDAR-dependent long-term potentiation was assessed at the Schaffer collateral-CA1 synapse. In addition, we performed behavioral analyses using the open field and novel object recognition tasks.Results: NMDAR-dependent long-term potentiation in the hippocampal CA1 area was significantly suppressed, indicating successful NMDAR dysfunction in this subfield. Spontaneous locomotor activity as well as anxiety-related behavior in the open field did not differ between NMDAR-CSF-treated and control animals. In the novel object recognition task, there were no differences in the motivation to approach objects. In contrast, we observed a significantly preferred exploration of the novel object only in control, but not in NMDAR-CSF-treated rats.Conclusion: These results indicate that NMDAR dysfunction obtained by intrahippocampal stereotactic injection does not alter locomotor or anxiety-related behavior. In addition, approach to an object or exploratory behavior in general are not affected either, but intact initial NMDAR-dependent processes might be involved in novel object recognition.