Spinal cord injury (SCI) is a devastating medical condition that forever changes the trajectory of life. It is also costly to the health care system, similar to traumatic brain injury or Alzheimer’s. Perhaps surprisingly, people with SCI report autonomic (i.e., automatic/unconscious) issues such as cardiovascular dysfunction as a more important health issue than walking again. One of the most common autonomic dysfunctions after SCI is extreme blood pressure (BP) instability, where BP can swing to dangerously low and high levels. BP instability is common and can occur more than 65 times/day. These BP swings can cause cognitive decline, heart attack, stroke, loss-of-consciousness and death. In fact, cardiovascular disease is up to four times more common in SCI and is the most common cause of death. The primary reason for these BP swings is inappropriate changes to autonomic nervous circuit connections after SCI. As we do not fully-understand how these connections change, we do not have effective therapies for reducing BP instability. Our study aims to reveal with unprecedented accuracy the autonomic connections (i.e., in 3D using transparent tissue, genetically-modified animal strains, optogenetic manipulations, highly-specific tracing) and characterize how they change after SCI. We recently developed a novel biointegratable device targeting autonomic connections with electrical stimulation of the spinal cord (eSTIM), which based on previous work should be able to restore normal connections and function if applied over a long-period of time. As such, we will then test if we can restore normal autonomic connections by applying long-term daily eSTIM. We expect that eSTIM targeting autonomic connections will rehabilitate function and reduce BP instability. We are the only site in the world with the necessary tools and expertise to perform this study. We patented this technology and are working with neurosurgeons to rapidly translate this into a therapy.