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 Ca2+ 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:
已知去甲肾上腺素(去甲肾上腺素)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的程度,一种神经胶质细胞,参与小鼠初级视觉皮层(V1)的去甲肾上腺素能信号传导。星形胶质细胞是中枢神经系统中神经元的重要伙伴。它们是大脑稳态的核心,而且还动态调节神经元活动,特别是通过中继和调节神经调质信号。的确,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能信号传导的程度尚不清楚.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节,我们采用短发夹RNA介导的敲低以及星形胶质细胞中主要去甲肾上腺素受体的药理学操作,α1A-肾上腺素受体。用急性脑切片,我们发现星形胶质细胞α1A-肾上腺素受体亚型有助于视觉皮层星形胶质细胞中大量细胞内Ca2+信号的产生,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-肾上腺素受体信号传导的减少是否影响V1中神经元回路的功能,我们使用了膜片钳和场电位记录。这些表明,通过星形胶质细胞α1A-肾上腺素受体的去甲肾上腺素能信号传导不仅对于调节突触活动,而且通过增强视觉信息处理中涉及的回路中的突触反应来调节V1的可塑性非常重要。