Structural and functional remodeling surrounding electrodes implanted in the brain

Abstract: By stimulating or recording electrical activity, microelectrode arrays implanted in the brain have created a renaissance in the treatment of neurological diseases and injuries. Likewise, these devices are an enabling technology to understand normal brain function and behavior. However, questions remain regarding the relationship between the biological response to implanted electrodes, their chronic performance, and features of their design. It is my lab’s goal to understand the basic science underlying the interaction between implanted electrodes and brain cells, and to provide guiding principles to improve device design and performance as a result. Recently, we have found novel effects of implanted silicon and polyimide-based electrode arrays on the structure and function of local neurons, including alterations in ion channel expression, synaptic transporter expression, dendritic spine density, and excitability. Results of quantitative immunohistochemistry demonstrate a progressive local increase in the expression of potassium ion channels and inhibitory transporters surrounding devices implanted in the brains of rats over time, indicating a potential shift toward hypoexcitability over the 6- week time course studied. Two-photon laser scanning microscopy in brain slice preparations revealed profound local spine loss surrounding implants, coupled with observations of reduced responsiveness to injected current during whole cell intracellular recordings, where preliminary observations indicate pronounced effects surrounding traditional silicon-based devices. More recently, RNA-sequencing has complemented our understanding of these observed plasticity effects, where a current goal is to characterize molecular identity and function of neurons and non-neurons surrounding implanted electrodes. Our results suggest a novel role of local plasticity surrounding devices in chronic signal loss and instability, and we are currently working to assess and perturb local gene expression to reveal potential underlying mechanisms.

Bio: Dr. Erin Purcell received her bachelor’s degree in biomedical engineering from Michigan Technological University in 2001. She earned her doctoral degree in 2008 under the guidance of Dr. Daryl Kipke at the University of Michigan, where her work focused on developing ways to improve the integration of neural implants with the surrounding brain tissue. Following graduation, Erin joined the Kresge Hearing Research Institute as a Research Fellow in Dr. Keith Duncan's laboratory at the University of Michigan, where she trained in intracellular (patch clamp) neural recordings. Erin joined the faculty at Michigan State University in 2014 and was tenured as an associate professor in the Departments of Electrical and Computer Engineering and Biomedical Engineering in 2020. As the P.I. of the Regenerative Electrode Interface Lab, Dr. Purcell is pursuing new approaches to characterize, modulate, and regenerate neuronal responses at the interface of electrodes implanted in the brain. The lab is funded by two NIH R01 awards and an NSF CAREER award.

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