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Network-level encoding of local neurotransmitters in cortical astrocytes
Nature ( IF 64.8 ) Pub Date : 2024-04-17 , DOI: 10.1038/s41586-024-07311-5
Michelle K. Cahill , Max Collard , Vincent Tse , Michael E. Reitman , Roberto Etchenique , Christoph Kirst , Kira E. Poskanzer

Astrocytes, the most abundant non-neuronal cell type in the mammalian brain, are crucial circuit components that respond to and modulate neuronal activity through calcium (Ca2+) signalling1,2,3,4,5,6,7. Astrocyte Ca2+ activity is highly heterogeneous and occurs across multiple spatiotemporal scales—from fast, subcellular activity3,4 to slow, synchronized activity across connected astrocyte networks8,9,10—to influence many processes5,7,11. However, the inputs that drive astrocyte network dynamics remain unclear. Here we used ex vivo and in vivo two-photon astrocyte imaging while mimicking neuronal neurotransmitter inputs at multiple spatiotemporal scales. We find that brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca2+ responses beyond an individual stimulated cell. Further, we find that a key subset of Ca2+ activity—propagative activity—differentiates astrocyte network responses to these two main neurotransmitters, and may influence responses to future inputs. Together, our results demonstrate that local, transient neurotransmitter inputs are encoded by broad cortical astrocyte networks over a minutes-long time course, contributing to accumulating evidence that substantial astrocyte–neuron communication occurs across slow, network-level spatiotemporal scales12,13,14. These findings will enable future studies to investigate the link between specific astrocyte Ca2+ activity and specific functional outputs, which could build a consistent framework for astrocytic modulation of neuronal activity.



中文翻译:

皮质星形胶质细胞局部神经递质的网络级编码

星形胶质细胞是哺乳动物大脑中最丰富的非神经元细胞类型,是通过钙 (Ca 2+ ) 信号传导响应和调节神经元活动的重要电路组件1,2,3,4,5,6,7。星形胶质细胞 Ca 2+活性具有高度异质性,发生在多个时空尺度上——从快速、亚细胞活动3,4到连接星形胶质细胞网络中缓慢、同步的活动8,9,10——影响许多过程5,7,11。然而,驱动星形胶质细胞网络动态的输入仍不清楚。在这里,我们使用离体和体内双光子星形胶质细胞成像,同时在多个时空尺度上模拟神经元神经递质输入。我们发现,GABA 和谷氨酸的短暂亚细胞输入会导致星形胶质细胞广泛、持久的 Ca 2+反应,超出单个受刺激细胞的范围。此外,我们发现 Ca 2+活性的一个关键子集——增殖活性——区分了星形胶质细胞网络对这两种主要神经递质的反应,并可能影响对未来输入的反应。总之,我们的结果表明,局部的、短暂的神经递质输入是由广泛的皮质星形胶质细胞网络在长达几分钟的时间过程中编码的,有助于积累证据,表明大量的星形胶质细胞-神经元通信发生在缓慢的网络级时空尺度上12,13,14。这些发现将使未来的研究能够调查特定星形胶质细胞 Ca 2+活性和特定功能输出之间的联系,这可以为星形胶质细胞神经元活动调节建立一致的框架。

更新日期:2024-04-17
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