Electrical microstimulation has become a mainstay of fundamental neuroscience exploration and an increasingly prevalent clinical therapy. Despite the growing prevalence of neuromodulation therapies, the fundamental physiological and mechanistic properties driving the beneficial effect for the patient are poorly understood. This project aims to greatly improve our understanding of how different non-neuronal cells (myeloid lineage, oligodendrocyte progenitor lineage, and vascular smooth muscle cells) respond and contribute to the electrical stimulation response. Understanding of the relationship between stimulation parameters and supporting non-neuronal cell activity, including blood flow, will help determine the impact of electrical microstimulation on chronic circuit behavior in-vivo over time. In this project, we use leading-edge in vivo multiphoton imaging techniques with multiple transgenic animals to systematically evaluate the relationship between stimulation parameters and the induced changes over time at the molecular, cellular, and local network. An improved understanding of the impact of electrical microstimulation on the overall tissue health, changes to the foreign body response, stimulation of tissue repair, and safety limits will help inform improved stimulation paradigms and device design for therapeutic applications and basic neuroscience research.
We also aim to advance our understanding of how electrical and optogenetic stimulation alters spatial and temporal interactions in the nervous system across molecular, cellular, and network levels. Understanding of the relationship between stimulation parameters, excitatory and inhibitory network activity, tissue safety, and its impact on chronic circuit behavior and tissue excitability in-vivo have been historically limited by the sensitivity and specificity of in-vivo measurement techniques. An improved understanding of the impact of electrical stimulation on overall tissue health will help improve stimulation paradigms and device design for therapeutic applications and basic neuroscience research. For example, imbalances in excitatory and inhibitory neuronal activity have been indicated as a crucial component of many neurological diseases, such as autism spectrum disorder, stroke and traumatic brain injuries. Lastly, in human brain-computer interface applications, the ability to stimulate distinct spatiotemporal patterns of neurons with the same electrode may uncover the ability to evoke multiple sensations with the same permanently implanted microelectrodes.