Optical excitation and detection of neuronal activity

TL;DR

This paper introduces a novel, label-free phase imaging technique to detect neuronal activity induced by optogenetics, overcoming limitations of traditional electrophysiology and fluorescence methods.

Contribution

The study develops a multimodal instrument that combines high-resolution stimulation with nanometer-scale detection of intracellular transport changes in neurons.

Findings

Optical pathlength fluctuations correlate with active organelle transport.

Transport velocity distribution broadens significantly in stimulated cells.

The method provides a contactless way to measure optogenetic responses.

Abstract

Optogenetics has emerged as an exciting tool for manipulating neural activity, which in turn, can modulate behavior in live organisms. However, detecting the response to the optical stimulation requires electrophysiology with physical contact or fluorescent imaging at target locations, which is often limited by photobleaching and phototoxicity. In this paper, we show that phase imaging can report the intracellular transport induced by optogenetic stimulation. We developed a multimodal instrument that can both stimulate cells with high spatial resolution and detect optical pathlength changes with nanometer scale sensitivity. We found that optical pathlength fluctuations following stimulation are consistent with active organelle transport. Furthermore, the results indicate a broadening in the transport velocity distribution, which is significantly higher in stimulated cells compared to optogenetically inactive cells. It is likely that this label-free, contactless measurement of optogenetic response will provide an enabling approach to neuroscience.