Cortex-wide neural interfacing via transparent polymer skulls

Leila Ghanbari,Anant Naik,Kevin W Eliceiri,Judith Dominguez,Sarah L West,Russell E Carter,Jia Hu,Nahom Mossazghi,Madelyn M Gray,Timothy J Ebner,Md Abdul Kader Sagar,Gang Chen,Lenora Haltom,Mathew L Rynes,Suhasa B Kodandaramaiah

doi:10.1038/s41467-019-09488-0

Leila Ghanbari, Anant Naik + Show 13 more

Open Access

https://doi.org/10.1038/s41467-019-09488-0

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Abstract

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. Progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. We engineered ‘See-Shells’—digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>300 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm deep. See-Shells allow calcium imaging from multiple, non-contiguous regions across the cortex. Perforated See-Shells enable introducing penetrating neural probes to perturb or record neural activity simultaneously with whole cortex imaging. See-Shells are constructed using common desktop fabrication tools, providing a powerful tool for investigating brain structure and function.

Highlights

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors
We introduce See-Shells, digitally designed and morphologically realistic transparent polymer skulls that can be chronically implanted for long durations (>300 days) and allow optical access to 45 mm[2] of the dorsal cerebral cortex
The interpolated surface from a single mouse skull served as a template to digitally design generalized transparent skulls (See-Shells) using computer-aided design (CAD) software

Summary

Introduction

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. See-Shells are constructed using common desktop fabrication tools, providing a powerful tool for investigating brain structure and function Understanding these large-scale computations requires the ability to monitor and perturb neural activity across large regions of the cortex. The advent of streamlined strategies to rapidly generate transgenic mice expressing optical reporters has been matched by the recent development of wide-field 2P imaging approaches[8,9,10] Deploying these new optical tools and instrumentation for chronic imaging of large areas of the cerebral cortex requires replacing the overlying opaque skull with a transparent substrate. Curved glass windows and associated surgical implantation methodology were introduced that allow chronic optical access to the whole dorsal cortex for cellular resolution imaging[14] While each of these approaches has advanced the field, each has limitations. See-Shells can be inexpensively fabricated using desktop prototyping tools and can be implanted using methodologies adapted from standard cranial window implantation procedures

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