Polymer Skulls With Integrated Transparent Electrode Arrays for Cortex-Wide Opto-Electrophysiological Recordings

Electrophysiology and optical imaging provide complementary neural sensing capabilities – electrophysiological recordings have high temporal resolution, while optical imaging allows recording of genetically-defined populations at high spatial resolution. Combining these two modalities for simultaneous large-scale, multimodal sensing of neural activity across multiple brain regions can be very powerful. Here, transparent, inkjet-printed electrode arrays with outstanding optical and electrical properties are seamlessly integrated with morphologically conformant transparent polymer skulls. Implanted on transgenic mice expressing the Calcium (Ca²⁺) indicator GCaMP6f in excitatory neurons, these “eSee-Shells” provide a robust opto-electrophysiological interface for over 100 days. eSee-Shells enable simultaneous mesoscale Ca²⁺ imaging and electrocorticography (ECoG) acquisition from multiple brain regions covering 45 mm² of cortex under anesthesia and in awake animals. The clarity and transparency of eSee-Shells allow recording single-cell Ca²⁺ signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca²⁺ signals that depend on the behavioral state.