Neuronal synaptic architecture revealed by cryo-correlative light and electron microscopy

• Published in: Biophysics reports Vol. 11; no. 3; pp. 198 - 208
• Main Authors: Wang, Pei, Tian, Buyun, Xu, Xiaojun, Luan, Huiqin, zhang, Yan, Sun, Wenhao, Hu, Liqiao, Li, Yuanyuan, Yao, Yuchen, Li, Weixing, Zhang, Shuli, Li, Xia, Feng, Wei, Ji, Wei, Xue, Yanhong
• Format: Journal Article
• Language: English
• Published: China Biophysics Reports Editorial Office 30.06.2025
• Subjects: Cryo-ET; Cryo-CLEM; Synaptic cleft; Synapse structure; Presynaptic
• ISSN: 2364-3439; 2364-3420; 2364-3420
• DOI: 10.52601/bpr.2024.240035

Cryo-correlative light and electron microscopy (cryo-CLEM) is a powerful technique that combines fluorescence imaging for specific localization with electron microscopy for detailed structural analysis, enabling high-resolution exploration of synaptic structures in neurons. In this study, we employed a cryo-CLEM approach using three independent alignment markers to precisely correlate electron microscopy (EM) images with light microscopy (LM) images of neuronal synapses under cryogenic conditions. This methodology revealed a distinctive pattern of electron densities in the synaptic clefts. Additionally, we were able to capture high-resolution images of presynaptic vesicles in various states, underscoring the potential of cryo-CLEM in advancing synaptic research.