Optical Electrophysiology: Toward the Goal of Label-Free Voltage Imaging

Measuring and monitoring the electrical signals transmitted between neurons is key to understanding the communication between neurons that underlies human perception, information processing, and decision-making. While electrode-based electrophysiology has been the gold standard, optical electrophysiology has opened up a new area in the past decade. Voltage-dependent fluorescent reporters enable voltage imaging with high spatial resolution and flexibility to choose recording locations. However, they exhibit photobleaching as well as phototoxicity and may perturb the physiology of the cell. Label-free optical electrophysiology seeks to overcome these hurdles by detecting electrical activities optically, without the incorporation of exogenous fluorophores in cells. For example, electrochromic optical recording detects neuroelectrical signals via a voltage-dependent color change of extracellular materials, and interferometric optical recording monitors membrane deformations that accompany electrical activities. Label-free optical electrophysiology, however, is in an early stage, and often has limited sensitivity and temporal resolution. In this Perspective, we review the recent progress to overcome these hurdles. We hope this Perspective will inspire developments of label-free optical electrophysiology techniques with high recording sensitivity and temporal resolution in the near future.

Automated summary

Electrophysiology is crucial for studying neuronal communication, with optical electrophysiology emerging as a new technique for detecting electrical activities without the use of fluorophores. However, current label-free optical electrophysiology techniques are still in early stages and face limitations in sensitivity and temporal resolution. Further progress is needed to develop techniques with higher recording sensitivity and temporal resolution in the future.