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基于谷氨酸能、γ-氨基丁酸能和儿茶酚胺能受体密度,对沿背腹轴的小鼠海马体进行新的边界划分和分离。

New boundaries and dissociation of the mouse hippocampus along the dorsal-ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities.

机构信息

C. & O. Vogt-Institute for Brain Research, Medical Faculty, University Clinic Düsseldof, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.

Institute of Neuroscience and Medicine INM-1, Research Centre Jülich, 52425, Jülich, Germany.

出版信息

Hippocampus. 2021 Jan;31(1):56-78. doi: 10.1002/hipo.23262. Epub 2020 Sep 28.

Abstract

In rodents, gene-expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, the intermediate and the ventral hippocampal formation (HF) are distinct entities. These findings are underpinned by behavioral studies showing a dissociable role of dorsal and ventral HF in learning, memory, stress and emotional processing. However, up to now, the molecular basis of such differences in relation to discrete boundaries is largely unknown. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA, kainate and mGluR , GABAergic GABA (including benzodiazepine binding sites), GABA , dopaminergic D and noradrenergic α and α receptors as key modulators for signal transmission in hippocampal functions, using quantitative in vitro receptor autoradiography along the dorsal-ventral axis of the mouse HF. Beside general different receptor profiles of the dentate gyrus (DG) and Cornu Ammonis fields (CA1, CA2, CA3, CA4/hilus), we detected substantial differences between dorsal, intermediate and ventral subdivisions and individual layers for all investigated receptor types, except GABA . For example, striking higher densities of α receptors were detected in the ventral DG, while the dorsal DG possesses higher numbers of kainate, NMDA, GABA and D receptors. CA1 dorsal and intermediate subdivisions showed higher AMPA, NMDA, mGluR , GABA , D receptors, while kainate receptors are higher expressed in ventral CA1, and noradrenergic α and α receptors in the intermediate region of CA1. CA2 dorsal was distinguished by higher kainate, α and α receptors in the intermediate region, while CA3 showed a more complex dissociation. Our findings resulted not only in a clear segmentation of the mouse hippocampus along the dorsal-ventral axis, but also provides insights into the neurochemical basis and likely associated physiological processes in hippocampal functions. Therein, the presented data has a high impact for future studies modeling and investigating dorsal, intermediate and ventral hippocampal dysfunction in relation to neurodegenerative diseases or psychiatric disorders.

摘要

在啮齿动物中,基因表达、神经元调谐、连接和神经发生研究表明,背侧、中间和腹侧海马结构(HF)是不同的实体。这些发现得到了行为研究的支持,这些研究表明背侧和腹侧 HF 在学习、记忆、应激和情绪处理中具有可分离的作用。然而,到目前为止,关于离散边界的这种差异的分子基础在很大程度上是未知的。因此,我们使用定量体外受体放射自显影技术,沿着小鼠 HF 的背-腹轴分析了谷氨酸能 AMPA、NMDA、海人藻酸和 mGluR、GABA 能 GABA(包括苯二氮䓬结合位点)、GABA、多巴胺能 D 和去甲肾上腺素能 α 和 α 受体的结合位点密度,这些受体是海马功能中信号传递的关键调节剂。除了齿状回(DG)和 Cornu Ammonis 场(CA1、CA2、CA3、CA4/海马体)的一般不同受体谱外,我们还检测到所有研究的受体类型在背、中和腹部分区和个别层之间存在显著差异,除了 GABA 之外。例如,在腹侧 DG 中检测到更高密度的 α 受体,而在背侧 DG 中则具有更高数量的海人藻酸、NMDA、GABA 和 D 受体。CA1 背侧和中间部分显示出更高的 AMPA、NMDA、mGluR、GABA、D 受体,而海人藻酸受体在腹侧 CA1 中表达更高,去甲肾上腺素能 α 和 α 受体在 CA1 的中间区域表达更高。CA2 背侧在中间区域表现出更高的海人藻酸、α 和 α 受体,而 CA3 则表现出更为复杂的分离。我们的研究结果不仅使小鼠海马体沿着背-腹轴进行了清晰的分割,还提供了对海马体功能中神经化学基础和可能相关生理过程的深入了解。其中,所呈现的数据对未来研究具有重要影响,这些研究涉及与神经退行性疾病或精神障碍相关的背侧、中间和腹侧海马体功能障碍的建模和研究。

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