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.

Wide-Field Calcium Imaging of Dynamic Cortical Networks during Locomotion.

Motor behavior results in complex exchanges of motor and sensory information across cortical regions. Therefore, fully understanding the cerebral cortex's role in motor behavior requires a mesoscopic-level description of the cortical regions engaged, their functional interactions, and how these functional interactions change with behavioral state. Mesoscopic Ca2+ imaging through transparent polymer skulls in mice reveals elevated activation of the dorsal cerebral cortex during locomotion. Using the correlations between the time series of Ca2+ fluorescence from 28 regions (nodes) obtained using spatial independent component analysis (sICA), we examined the changes in functional connectivity of the cortex from rest to locomotion with a goal of understanding the changes to the cortical functional state that facilitate locomotion. Both the transitions from rest to locomotion and from locomotion to rest show marked increases in correlation among most nodes. However, once a steady state of continued locomotion is reached, many nodes, including primary motor and somatosensory nodes, show decreases in correlations, while retrosplenial and the most anterior nodes of the secondary motor cortex show increases. These results highlight the changes in functional connectivity in the cerebral cortex, representing a series of changes in the cortical state from rest to locomotion and on return to rest.