Validation of transparent and flexible neural implants for simultaneous electrophysiology, functional imaging, and optogenetics

Abstract

The combination of electrophysiology and neuroimaging methods allows the simultaneous measurement of electrical activity signals with calcium dynamics from single neurons to neuronal networks across distinct brain regions in vivo. While traditional electrophysiological techniques are limited by photo-induced artefacts and optical occlusion for neuroimaging, different types of transparent neural implants have been proposed to resolve these issues. However, reproducing proposed solutions is often challenging and it remains unclear which approach offers the best properties for long-term chronic multimodal recordings. We therefore created a streamlined fabrication process to produce, and directly compare, two types of transparent surface micro-electrocorticography (μECoG) implants: nano-mesh gold structures (m-μECoGs) versus a combination of solid gold interconnects and PEDOT:PSS-based electrodes (pp-μECoGs). Both implants allowed simultaneous multimodal recordings but pp-μECoGs offered the best overall electrical, electrochemical, and optical properties with negligible photo-induced artefacts to light wavelengths of interest. Showing functional chronic stability for up to four months, pp-μECoGs also allowed the simultaneous functional mapping of electrical and calcium neural signals upon visual and tactile stimuli during widefield imaging. Moreover, recordings during two-photon imaging showed no visible signal attenuation and enabled the correlation of network dynamics across brain regions to individual neurons located directly below the transparent electrical contacts.