Neuroprostheses are devices implanted in the brain that record or stimulate the electrical activity of nearby neurons. These devices hold tremendous potential for breakthroughs in advanced research and clinical applications. Despite the rapid growth in the use of these technologies, certain aspects of their influence on surrounding neurons, and the reasons underlying their often unpredictable function over time, remain unclear. In this study, we explore the effects of implanted neuroprostheses on the excitability of neurons at the device interface. We hypothesize that the insertion trauma and inflammatory response initiated by neuroprosthesis implantation will impact the ion channel expression and intrinsic excitability of local neurons. This is expected to result in an initial period of hyperexcitability followed by a period of relative hypoexcitability, where effects will be evident in whole-cell recordings and quantitative immunohistochemistry of ion channel expression. A novel approach for assaying the intrinsic excitability of neurons surrounding devices is developed, where whole-cell voltage- and current-clamp recordings are taken from neurons surrounding silicon devices contained in brain tissue slices collected following implantation in rats. This preparation will provide detailed information on the biophysical characteristics of neurons at the device interface, clear visual targeting of specific cell types for recordings, and correlating outcomes to local glial densities in subsequent histology. In separate subjects, ion channel expression will be quantitatively assessed at time points spanning twelve weeks surrounding devices implanted in the rat brain, where specific classes of voltage-gated sodium and potassium channels are surveyed. These studies will open up a new understanding of plasticity changes induced by the presence of devices implanted in the brain, focused on impacts to the intrinsic excitability of the cells that neuroprostheses electrically interface. The understanding gained will inform a variety of phenomena related to neuroprosthesis function, including observations of instability and variability in recording quality, responsiveness to stimulation, and placebo effects after device implantation. The research impacts a broad range of implanted devices which read-out or write-in neural activity, and future work will leverage the knowledge gained to improve long-term device function.
Neural implants hold tremendous therapeutic potential for patients suffering from the debilitating effects of neurological injury and disease. However, understanding of the mode of action and failure mechanisms of these devices remains incomplete. Our study seeks to understand the effects of neural implants on the function of neurons at the device interface, broadly impacting the future development and study of neural prostheses.
| Salatino, Joseph W; Ludwig, Kip A; Kozai, Takashi D Y et al. (2017) Glial responses to implanted electrodes in the brain. Nat Biomed Eng 1:862-877 |
| Salatino, Joseph W; Winter, Bailey M; Drazin, Matthew H et al. (2017) Functional remodeling of subtype-specific markers surrounding implanted neuroprostheses. J Neurophysiol 118:194-202 |
