Transparent Thiol‐ene/Acrylate‐Based MicroECoG Devices Used for Concurrent Recording of Fluorescent Calcium Signals and Electrophysiology in Awake Animals

Abstract

voltage-sensitive dye imaging catalyzed the development of transparent neural interfaces that enable the application of both modalities. Electrophysiological methods with high temporal resolution are therefore often used in parallel with a non-invasive optical method with high spatial resolution. [2] Electrocorticogram (ECoG) register neural activity on the cortical surface, circumventing the electrical insulation of the scalp with minimally invasive surgical intervention. [3] By using of ECoG instead of the non-invasive electroencephalography (EEG) the difficulty to achieve efficient electrodeskin impedance [4] can be overcome. Twophoton microscopy is a laser-scanning, multifocal technique that typically collects fluorescent light from a single location. [5] Since two photons combine their energy during measurement, they are less harmful to biological tissues than the single-photon techniques. The two-photon calcium imaging is an efficient way to monitor the calcium-binding kinetics with a highly precise morphological image. [6] This method uses the fact, that in the living cells most of the depolarizing signals are in connection with the Ca 2+ influx, because of the voltagegated Ca 2+ channels. [7] Optogenetics provides molecular tools to selectively manipulate neuronal activity with light. [8] This technique uses genetic engineering to insert photosensitive protein channels into a specific population of neurons. [9] Shape memory polymers (SMPs) are suitable substrate materials for soft neural interfaces due to their tunable elastic characteristics. The stability and biocompatibility of intracortical SMP probes are demonstrated. In this work, a SMP-based cortical implant capable of recording high-density micro-electrocorticography is utilized in a multimodal neuroimaging scheme. The transparent nature of thiol-ene/acrylate substrate is exploited, and the feasibility of measuring intracranial electroencephalogram and fluorescent GCaMP6 signals with two-photon imaging through the device is presented in mice. The potential influence of the optical properties of the microdevice is investigated using fluorescent microbeads, hippocampal brain slices, and awake animals. It is found that neurites and cell soma can be efficiently detected with sufficient resolution to follow changes in the calcium signal. These chronically implanted devices do not suppress the quality of optical signals exceeding 22 weeks after implantation. These results indicate that thiol-ene/acrylate ECoG is an appropriate tool to combine electrophysiology with two-photon imaging while leveraging the inherent tissue-friendly properties of SMPs.

Implantable neural electrodes: from preparation optimization to application

“…50 When the material is applied in the preparation of a nerve electrode, the electrode can be softened and deformed under physiological conditions. The Young's modulus of a thiol–ene/acrylate neural probe softening from 2 Gpa to 300 Mpa was presented by Ágnes Szabó et al 51 Taylor et al prepared neural cuff electrodes with a three-dimensional (3D) soft substrate using thiol–ene/acrylate-shape memory polymers. The electrode could be inserted under the nerve in a flat state, softened, and wrapped around the nerve when reaching the physiological condition, and could effectively stimulate nerve activity (Fig.…”