Correlative voltage imaging and cryo-electron tomography bridge neuronal activity and molecular structure

Mingyu Jung, Gwanho Ko, Dongsung Lim, Seonghoon Kim, Sojeong Kim, Young-Joon Kim, Myunghwan Choi () and Soung-Hun Roh ()
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Mingyu Jung: Seoul National University
Gwanho Ko: Seoul National University
Dongsung Lim: Seoul National University
Seonghoon Kim: Seoul National University
Sojeong Kim: Gachon University
Young-Joon Kim: Gachon University
Myunghwan Choi: Seoul National University
Soung-Hun Roh: Seoul National University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Neurons exhibit varying electrophysiological properties due to dynamic changes in spatiotemporal molecular networks. In situ cryo-electron tomography (cryo-ET) provides advantages for high-resolution visualization of macromolecular complexes within their cellular context. Although correlation with fluorescent labeling allows cryo-ET to target specific cellular regions, it does not adequately reflect the electrophysiological properties of heterogeneous neurons. To bridge high-resolution molecular imaging with electrophysiological properties of individual neurons, we develop a Correlative Voltage Imaging and cryo-ET (CoVET) technique. The nondestructive nature of voltage imaging is compatible with cryo-ET, enabling a direct correlation between neuronal electrophysiology and molecular structures. Neurons are clustered based on their electrophysiological properties, allowing for single-cell-guided structural analysis using cryo-ET. We analyze the translational landscapes of individual neurons and find distinct structural characteristics and spatial networks among ribosomes from different electrophysiological clusters. Our results highlight the importance of the correlation between the electrophysiological properties and molecular structures.

Date: 2025
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DOI: 10.1038/s41467-025-64431-w

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