阿尔茨海默病 3xTg 小鼠模型中 VIP 中间神经元点燃输出的改变和 CA1 海马环路的早期功能障碍

IF 6.4 1区 生物学 Q1 BIOLOGY
Felix Michaud, Ruggiero Francavilla, Dimitry Topolnik, Parisa Iloun, Suhel Tamboli, Frederic Calon, Lisa Topolnik
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引用次数: 0

摘要

阿尔茨海默病(AD)会导致记忆力逐渐衰退,而海马功能的改变是人类和动物研究中最早观察到的病理特征之一。海马内的 GABA 能中间神经元(IN)协调网络活动,其中表达血管活性肠肽和钙网蛋白的 3 型中间神经元特异性(I-S3)细胞起着至关重要的作用。这些细胞主要为海马 CA1 区的主要兴奋细胞(PC)提供抑制,调节输入和记忆形成。然而,目前还不清楚AD病理是否会诱导I-S3细胞的活动发生变化,从而影响海马的网络结构。在这里,我们利用年轻的成年 3xTg-AD 小鼠发现,虽然 I-S3 细胞的密度和形态未受影响,但它们的发射输出发生了显著变化。具体来说,I-S3 细胞的动作电位延长,发射率降低,这与 CA1 INs 的抑制作用减弱以及它们在空间决策和物体探索任务中被更多招募有关。此外,CA1 PC 的激活也受到了影响,这表明 CA1 网络功能的早期破坏。这些研究结果表明,I-S3细胞点燃模式的改变可能会引发海马CA1回路的早期功能障碍,从而可能影响AD病理学的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease
Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal CA1 region, regulating incoming inputs and memory formation. However, it remains unclear whether AD pathology induces changes in the activity of I-S3 cells, impacting the hippocampal network motifs. Here, using young adult 3xTg-AD mice, we found that while the density and morphology of I-S3 cells remain unaffected, there were significant changes in their firing output. Specifically, I-S3 cells displayed elongated action potentials and decreased firing rates, which was associated with a reduced inhibition of CA1 INs and their higher recruitment during spatial decision-making and object exploration tasks. Furthermore, the activation of CA1 PCs was also impacted, signifying early disruptions in CA1 network functionality. These findings suggest that altered firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.
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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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