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星形胶质细胞 α1A-肾上腺素受体是小鼠视觉皮层神经调质系统的关键组成部分。

The astrocyte α1A-adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex.

机构信息

Laboratory of Glia Biology, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium.

Department of Neurosciences, KU Leuven, Leuven, Belgium.

出版信息

Glia. 2024 Nov;72(11):1955-1973. doi: 10.1002/glia.24591. Epub 2024 Jul 12.

Abstract

Noradrenaline (norepinephrine) is known to modulate many physiological functions and behaviors. In this study, we tested to what extent astrocytes, a type of glial cell, participate in noradrenergic signaling in mouse primary visual cortex (V1). Astrocytes are essential partners of neurons in the central nervous system. They are central to brain homeostasis, but also dynamically regulate neuronal activity, notably by relaying and regulating neuromodulator signaling. Indeed, astrocytes express receptors for multiple neuromodulators, including noradrenaline, but the extent to which astrocytes are involved in noradrenergic signaling remains unclear. To test whether astrocytes are involved in noradrenergic neuromodulation in mice, we employed both short hairpin RNA mediated knockdown as well as pharmacological manipulation of the major noradrenaline receptor in astrocytes, the α1A-adrenoreceptor. Using acute brain slices, we found that the astrocytic α1A-adrenoreceptor subtype contributes to the generation of large intracellular Ca signals in visual cortex astrocytes, which are generally thought to underlie astrocyte function. To test if reduced α1A-adrenoreceptor signaling in astrocytes affected the function of neuronal circuits in V1, we used both patch-clamp and field potential recordings. These revealed that noradrenergic signaling through the astrocyte α1A-adrenoreceptor is important to not only modulate synaptic activity but also to regulate plasticity in V1, through the potentiation of synaptic responses in circuits involved in visual information processing.

摘要

去甲肾上腺素(noradrenaline)已知可调节许多生理功能和行为。在这项研究中,我们测试了星形胶质细胞(一种神经胶质细胞)在小鼠初级视觉皮层(V1)的去甲肾上腺素信号中参与的程度。星形胶质细胞是中枢神经系统中神经元的重要伙伴。它们是脑内稳态的核心,但也动态地调节神经元活动,特别是通过传递和调节神经调质信号。事实上,星形胶质细胞表达多种神经调质的受体,包括去甲肾上腺素,但星形胶质细胞参与去甲肾上腺素信号的程度尚不清楚。为了测试星形胶质细胞是否参与小鼠的去甲肾上腺素能神经调制,我们既采用短发夹 RNA 介导的敲低,也采用星形胶质细胞中主要去甲肾上腺素受体(α1A-肾上腺素能受体)的药理学操纵。使用急性脑切片,我们发现星形胶质细胞中的 α1A-肾上腺素能受体亚型有助于在视觉皮层星形胶质细胞中产生大的细胞内 Ca 信号,这通常被认为是星形胶质细胞功能的基础。为了测试星形胶质细胞中 α1A-肾上腺素能受体信号的减少是否影响 V1 中神经元回路的功能,我们使用了膜片钳和场电位记录。这些结果表明,通过星形胶质细胞的 α1A-肾上腺素能受体的去甲肾上腺素能信号不仅对调节突触活动很重要,而且对 V1 中的可塑性也很重要,通过增强涉及视觉信息处理的回路中的突触反应来实现。

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