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Updated: Nov 3, 2025

Transpupillary Two-Photon In Vivo Imaging of the Mouse Retina
Published on: February 13, 2021
Ultra-low Impedance Graphene Microelectrodes with High Optical Transparency for Simultaneous Deep 2-photon Imaging in
Yichen Lu1, Xin Liu1, Ryoma Hattori2
19500 Gilman Drive, Electrical and Computer Engineering Department, Jacobs School of Engineering, University of California, San Diego, La Jolla, California 92093, USA.
Abstract:
The last decades have witnessed substantial progress in optical technologies revolutionizing our ability to record and manipulate neural activity in genetically modified animal models. Meanwhile, human studies mostly rely on electrophysiological recordings of cortical potentials, which cannot be inferred from optical recordings, leading to a gap between our understanding of dynamics of microscale populations and brain-scale neural activity. By enabling concurrent integration of electrical and optical modalities, transparent graphene microelectrodes can close this gap. However, the high impedance of graphene constitutes a big challenge towards the widespread use of this technology. Here, we experimentally demonstrate that this high impedance of graphene microelectrodes is fundamentally limited by quantum capacitance. We overcome this quantum capacitance limit by creating a parallel conduction path using platinum nanoparticles. We achieve a 100 times reduction in graphene electrode impedance, while maintaining the high optical transparency crucial for deep 2-photon microscopy. Using a transgenic mouse model, we demonstrate simultaneous electrical recording of cortical activity with high fidelity while imaging calcium signals at various cortical depths right beneath the transparent microelectrodes. Multimodal analysis of Ca2+ spikes and cortical surface potentials offers unique opportunities to bridge our understanding of cellular dynamics and brain-scale neural activity.

