The astrocyte is a central glial cell and plays a critical role in the architecture and activity of neuronal circuits and brain functions through forming a tripartite synapse with neurons. Emerging evidence suggests that dysfunction of tripartite synaptic connections contributes to a variety of psychiatric and neurodevelopmental disorders. Furthermore, recent advancements with transcriptome profiling, cell biological and physiological approaches have provided new insights into the molecular mechanisms into how astrocytes control synaptogenesis in the brain. In addition to these findings, we have recently developed in vivo cell-surface proximity-dependent biotinylation (BioID) approaches, TurboID-surface and Split-TurboID, to comprehensively understand the molecular composition between astrocytes and neuronal synapses. These proteomic approaches have discovered a novel molecular framework for understanding the tripartite synaptic cleft that arbitrates neuronal circuit formation and function. Here, this short review highlights novel in vivo cell-surface BioID approaches and recent advances in this rapidly evolving field, emphasizing how astrocytes regulate excitatory and inhibitory synapse formation in vitro and in vivo.

星形胶质细胞是中央神经胶质细胞，通过与神经元形成三联突触，在神经元回路的结构和活动以及大脑功能中起着关键作用。新出现的证据表明，三方突触连接的功能障碍会导致各种精神和神经发育障碍。此外，转录组分析、细胞生物学和生理学方法的最新进展为星形胶质细胞如何控制大脑突触发生的分子机制提供了新的见解。除了这些发现，我们最近在体内开发了细胞表面接近依赖性生物素化 (BioID) 方法、TurboID 表面和 Split-TurboID，以全面了解星形胶质细胞和神经元突触之间的分子组成。这些蛋白质组学方法发现了一种新的分子框架，用于理解仲裁神经元回路形成和功能的三方突触间隙。在此，这篇简短的综述重点介绍了新的体内细胞表面 BioID 方法和这一快速发展领域的最新进展，强调了星形胶质细胞如何在体外和体内调节兴奋性和抑制性突触形成。