Project Summary/Abstract Implantable neurotechnology such as microelectrode arrays offers substantial promise to improve the condition of many neurogenerative diseases. However, shortly after implantation, foreign body response occurs, which is what researchers believe decreases stability and longevity of these devices. Established biomarkers such as glial acid fibrillary protein and astrogliosis and stimuli such as mechanical mismatch are studied to assess the state of response to the devices, however immune response in the brain is not well understood. Astrocytes play an important role in the brain’s immune system and recently, transcriptome analysis has confirmed calcium channel activity of reactive astrocytes to be a potential biomarker in many neurodegenerative diseases, in this dissertation project, I will investigate the correlation between astroglial reactivity and device features. Preliminary studies have demonstrated that calcium channel isoforms respond to different stimuli to induce the reactive state. I will use tissue co-culture methods to induce three types of inflammatory astrocytic models, and characterize each model’s reactivity to probe material stiffness, device features and change in cytoarchitecture, metabolism and pathophysiological genetic expression. I aim to elucidate that pathway in neuro foreign body response, which will give researchers a potential biomarker to target for therapeutic research concerning implantable neurotechnology. I have outlined the work done thus far, current and future training strategies for academic, professional, and educational advancement, as it relates to this project and aligns with this my career goals.

Projective Narrative The short-term goals of this project is to elucidate the effects of calcium channel expression on the reactive state of astrocytes, and its role in foreign body response to implantable neurotechnology. We further wish to expand on how mechanical properties and device features synergistically influences the astrocytic transcriptome. Long term, we wish to contribute to the body of knowledge in this field of neuroscience, characterizing calcium channel expression in reactive astrocytes, allowing therapeutic targeting of calcium channel expression to potentially improve the probe stability.