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

## TL;DR

Researchers developed a new method called CoVET to link the electrical activity of neurons with their molecular structures using voltage imaging and cryo-electron tomography.

## Contribution

The novel CoVET technique enables direct correlation between neuronal electrophysiology and molecular structures.

## Key findings

- CoVET allows clustering neurons based on electrophysiological properties for targeted structural analysis.
- Distinct structural and spatial features of ribosomes were observed among different electrophysiological clusters.
- The method bridges the gap between functional and structural analysis in neurons.

## 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.

The functional–structural link in neurons remains unclear despite its importance. Here, authors developed CoVET, a method combining voltage imaging with cryo-electron tomography to directly correlate neuronal function with molecular architecture.