A Spatial Transcriptomics Study of the Brain-Electrode Interface in Rat Motor Cortex

Abstract

AbstractThe study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental electrophysiology. After electrode implantation in the brain, microglial activation, reactive astrogliosis, and neuronal cell death create an environment immediately surrounding the electrode that is significantly altered from its homeostatic state. To uncover physiological changes potentially affecting device function and longevity, spatial transcriptomics was implemented in this preliminary study to identify changes in gene expression driven by electrode implantation. This RNA-sequencing technique (10x Genomics, Visium) uses spatially coded, RNA-binding oligonucleotides on a microscope slide to spatially identify each sequencing read. For these experiments, sections of rat motor cortex implanted with Michigan-style silicon electrodes were mounted on the Visium slide for processing. Each tissue section was labeled for neurons and astrocytes using immunohistochemistry to provide a spatial reference for mapping each sequencing read relative to the device tract. Results from rat motor cortex at 24 hours, 1 week, and 6 weeks post implantation showed up to 5811 differentially expressed genes between implanted and non-implanted tissue sections. Many of these genes are related to biological mechanisms previously reported in studies of the foreign body response to implanted electrodes, while others are novel to this study. These results will provide a foundation for future work to both improve and measure the effects of gene expression on the long-term stability of recordings from implanted electrodes in the brain. Ongoing work will expand on these initial observations as we gain a better understanding of the dynamic, molecular changes taking place in the brain in response to electrode implantation.