3D Printed Multifunctional Brain Windows for Simultaneous Optical Imaging and Electrophysiology

PROJECT SUMMARY
This proposal responds to PAR-18-870 titled “BRAIN Initiative: Development Optimization, and Validation of
Novel Tools and Technologies for Neuroscience Research (STTR).” This project is a Fast Track STTR with a
phase I and phase II. The small business, Applied Universal Dynamics Corp. (AUD) is collaborating with the
University of Minnesota (U of MN). The activity patterns of tens of millions of neurons – all organized into circuits
distributed across multiple brain regions mediate our interaction with the outside world. A mechanistic
understanding of the neuronal underpinnings of sensory perception, action, emotion, and cognition requires
measuring activities of these neuronal circuits at single cell resolution across several millimeters, and at multiple
temporal scales temporal scales. We propose to engineer and commercially disseminate transparent polymer
skulls that simultaneously allow wide-field optical neural sensing along with high temporal resolution electrical
recordings from the whole mammalian cortex. We will build on key technologies developed in in our laboratories.
Specifically, our collaborative has developed a methodology to design and fabricate transparent skulls (Brain
Windows) that allow sub-cellular resolution imaging of structure and function of the whole dorsal cortex in
behaving mice. In PHASE I of this proposal, we will first utilize 3-dimensional printing methodologies to
functionalize these transparent skulls with 8 channels of transparent electrocorticogram (ECoG) recording
electrodes (Aim 1). These devices will be utilized to perform simultaneous mesoscale calcium imaging and
ECoG recordings (Aim 2). In PHASE II of this proposal, we will refine the 3D printing methodology to realize
ultra-high density, transparent 128 channel ECoG arrays (Aim 1) for simultaneous whole cortex ECoG and
cellular resolution calcium imaging (Aim 2). Finally, we will engineer versions of the technology that allow
simultaneous extracellular recordings with surface ECoG and whole cortex optical imaging to realize a platform
that allows true 3D brain activity mapping (Aim 3).We propose to develop and commercially disseminate digitally generated, functionalized cranial prostheses
(`brain windowsandapos;) that synergistically combine wide‐field optical imaging with concurrent electrical recordings
of neuronal activities for widefield activity mapping of the whole cortex during behavior. These developments
will lead to fundamentally new experimental paradigms in mice and enable new insights into the neuronal
computations that underlie sensory perception, action and cognitive processes.