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 mm 2 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.
Bibliographical noteFunding Information:
S.B.K. acknowledges funds from the Mechanical Engineering department, College of Science and Engineering, MnDRIVE RSAM initiative of the University of Minnesota, McGovern Institute Neurotechnology (MINT) fund, National Institutes of Health (NIH) 1R21NS103098-01, and the Minnesota Department of Higher Education. M.L.R. was supported by 3R21 NS103098-01S1. L.G. was supported by the University of Minnesota Informatics Institute (UMII) Graduate Research fellowship. T.J.E. was supported, in part, from NIH grants RO1 NS18338 and R37 NS040389. K.W.E. acknowledges funding from DARPA grant N66001-17-2-4010. We would like to thank Bonita Van Heel at Minnesota Dental Research Center for Biomaterials and Biomechanics for help with micro-CT scanning experiments. We would also like to acknowledge Dr. Mark Sanders and Jason Mitchell at the UMN University Imaging Center where all 2P intensity imaging experiments were conducted. We also acknowledge Dr. Jenu Chacko and Dr. Jayne Squirrell of the UW-Madison who assisted with cell culture and viability experiments for FLIM.