Synapses are composed of thousands of proteins, providing the potential for extensive molecular diversity to shape synapse type-specific functional specializations. In this Review, we explore the landscape of synaptic diversity and describe the mechanisms that expand the molecular complexity of synapses, from the genotype to the regulation of gene expression to the production of specific proteoforms and the formation of localized protein complexes. We emphasize the importance of examining every molecular layer and adopting a systems perspective to understand how these interconnected mechanisms shape the diverse functional and structural properties of synapses. We explore current frameworks for classifying synapses and methodologies for investigating different synapse types at varying scales, from synapse-type-specific proteomics to advanced imaging techniques with single-synapse resolution. We highlight the potential of synapse-type-specific approaches for integrating molecular data with cellular functions, circuit organization and organismal phenotypes to enable a more holistic exploration of neuronal phenomena across different scales.

突触由数千种蛋白质组成，为广泛的分子多样性提供了塑造突触类型特异性功能特化的潜力。在这篇综述中，我们探讨了突触多样性的景观，并描述了扩展突触分子复杂性的机制，从基因型到基因表达的调节，再到特定蛋白质形式的产生和定位蛋白质复合物的形成。我们强调检查每个分子层并采用系统视角来了解这些相互关联的机制如何塑造突触的不同功能和结构特性的重要性。我们探讨了当前对突触进行分类的框架和在不同尺度上研究不同突触类型的方法，从突触类型特异性蛋白质组学到具有单突触分辨率的先进成像技术。我们强调了突触类型特异性方法将分子数据与细胞功能、回路组织和生物体表型相结合的潜力，以便能够更全面地探索不同尺度的神经元现象。