Project Summary This R01 (PA-20-185) application aims to greatly improve basic science understanding of oligodendrocytes with respect to spatial and temporal dynamic changes around chronically implanted microelectrodes and long- term recording performance. Penetrating recording microelectrode arrays are a crucial component of numerous human neuroprosthetics. Obtaining selective, high fidelity, long-lasting readouts of brain activity is a critical technology across basic and applied neuroscience that impacts motor, pre-motor, and visual cortex neuroprostheses and brain-computer interfaces. However, implantation of cortical microelectrodes causes a reactive tissue response, which results in a degradation of the preferred functional single-unit performance over time, thus limiting the device capabilities. While the BBB and the role of other glial cells like microglia and astrocytes have long been studied with respect to the degradation of chronic recording performance, the role of oligodendrocytes and oligodendrocyte progenitor in this foreign body response has been understudied. This proposal aims to characterize the role of oligodendrocytes and chronic recording failure in vivo caused by the insertion via quantifying structural, cellular, and molecular level tissue response to chronic implants in the brain in real time through combining multiphoton imaging technology and neural engineering technology at the University of Pittsburgh. A dynamic understanding of the interfaces is necessary for elucidating the mechanism(s) behind neural recording failure. Oligodendrocytes and oligodendrocyte progenitor cells have been implicated as key players in neuronal health following brain injury and numerous neurodegenerative diseases. Therefore, we will utilize transgenic animals with specific activity indicators in oligodendrocytes as well as pharmaceutical and gliomodulation approaches that target oligodendrocytes in order to explore mechanisms that improve oligodendrocyte health and chronic intracortical recording performance. This work has the potential to output basic and clinical science level knowledge relevant to neural engineering, ischemia, stroke, intracortical hemorrhage, aneurysm, traumatic brain injury, MS, ALS, and closed-loop neurostimulation.

Project Narrative Oligodendrocytes play an important role in a number of brain injuries and neurological diseases. This proposal details an innovative in vivo imaging technology to explore how these cell types cause negative tissue responses to intercortical microelectrodes in the cortex. Transgenic indicators, electrode design, pharmaceutical intervention strategies, and gliomodulation technologies will be examined to improve oligodendrocyte health and recording performance over time.