Fundamental properties of neurons and glia are distinctively different. Neurons are excitable cells that transmit information, whereas glia have long been considered as passive bystanders. Recently, the concept of tripartite synapse is proposed that glia are structurally and functionally incorporated into the synapse, the basic unit of information processing in the brains. It has then become intriguing how glia actively communicate with the presynaptic and postsynaptic compartments to influence the signal transmission. Here we present a thorough analysis at the transcriptional level on how glia respond to different types of neurotransmitters. Adult fly glia were purified from brains incubated with different types of neurotransmitters ex vivo. Subsequent RNA-sequencing analyses reveal distinct and overlapping patterns for these transcriptomes. Whereas Acetylcholine (ACh) and Glutamate (Glu) more vigorously activate glial gene expression, GABA retains its inhibitory effect. All neurotransmitters fail to trigger a significant change in the expression of their synthesis enzymes, yet Glu triggers increased expression of neurotransmitter receptors including its own and nAChRs. Expressions of transporters for GABA and Glutamate are under diverse controls from DA, GABA, and Glu, suggesting that the evoked intracellular pathways by these neurotransmitters are interconnected. Furthermore, changes in the expression of genes involved in calcium signaling also functionally predict the change in the glial activity. Finally, neurotransmitters also trigger a general metabolic suppression in glia except the DA, which upregulates a number of genes involved in transporting nutrients and amino acids. Our findings fundamentally dissect the transcriptional change in glia facing neuronal challenges; these results provide insights on how glia and neurons crosstalk in a synaptic context and underlie the mechanism of brain function and behavior.

中文翻译：

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通过 RNA 测序分析分析神经递质诱发的神经胶质反应

神经元和神经胶质细胞的基本特性截然不同。神经元是传递信息的兴奋细胞，而神经胶质细胞长期以来被认为是被动的旁观者。最近，提出了三方突触的概念，即神经胶质细胞在结构和功能上并入突触，突触是大脑中信息处理的基本单位。然后，神经胶质细胞如何主动与突触前和突触后区室通信以影响信号传输就变得有趣。在这里，我们在转录水平上对神经胶质细胞如何响应不同类型的神经递质进行了全面分析。从与不同类型的神经递质一起孵育的大脑中纯化出成年果蝇神经胶质细胞离体。随后的 RNA 测序分析揭示了这些转录组的独特且重叠的模式。乙酰胆碱 (ACh) 和谷氨酸 (Glu) 能更有效地激活神经胶质基因表达，而 GABA 则保留其抑制作用。所有神经递质都无法引发其合成酶表达的显着变化，但 Glu 会引发神经递质受体（包括其自身和 nAChR）的表达增加。GABA 和谷氨酸转运蛋白的表达受到 DA、GABA 和 Glu 的不同控制，表明这些神经递质诱发的细胞内通路是相互关联的。此外，参与钙信号传导的基因表达的变化也可以在功能上预测神经胶质细胞活性的变化。最后，神经递质还会引发神经胶质细胞中除 DA 之外的一般代谢抑制，DA 会上调许多涉及营养物质和氨基酸运输的基因。我们的研究结果从根本上剖析了神经胶质细胞面临神经元挑战时的转录变化；这些结果提供了关于神经胶质细胞和神经元如何在突触环境中串扰以及大脑功能和行为机制的见解。