Integration of Single-Photon Miniature Fluorescence Microscopy and Electrophysiological Recording Methods for in vivo Studying Hippocampal Neuronal Activity

Abstract

The miniature single-photon fluorescent microscope (miniscope) enables the visualization of calcium activity in vivo in freely moving laboratory animals, providing the capability to track cellular activity during the investigation of memory formation, learning, sleep, and social interactions. However, the use of calcium sensors for in vivo imaging is limited by their relatively slow (millisecond-scale) kinetics, which complicates the recording of high-frequency spike activity. The integration of methods from single-photon miniature fluorescent microscopy with electrophysiological recording, which possesses microsecond resolution, represents a potential solution to this issue. Such a combination of techniques allows for the simultaneous recording of optical and electrophysiological activity in a single animal in vivo. In this study, a flexible polyimide microelectrode was developed and integrated with the gradient lens of the miniscope. The in vivo tests conducted in this research confirmed that the microelectrode combined with the gradient lens facilitates simultaneous single-photon calcium imaging and local field potential recording in the hippocampus of an adult mouse.