Mapping Mechanosensory Circuits from the Bladder to Barrington's Nucleus

Project Summary: Detecting sensations from within our bodies, a process called interoception, is critical to drive many physiological processes. In the lower urinary tract, mechanosensory neurons monitor bladder fullness. Stretch from the bladder and urethra drives local and supraspinal reflex arcs for efficient urination, and the bladder fullness state is used by the central nervous system (CNS) to inform us of how urgent it will be to find a restroom. Furthermore, urination is a tightly controlled form of communication for many mammals, and humans control the urge to urinate until finding an appropriate time and place. Thus, the urinary tract switches between two modes: storage and voiding, and mechanical signals from the bladder are instructive, but not prescriptive for switching to a voiding mode. We will harness our knowledge of the micturition reflex pathway, and of the peripheral mechanisms of mechanosensation, to explore the precise brain circuits that encode bladder fullness and to map their dynamic activity patterns as the bladder fills. We will use immediate early gene activity, RNA sequencing techniques, fiber photometry and cellular-resolution calcium imaging to identify the CNS nuclei and cell types that respond to low versus high bladder stretch. By combining these tools with machine-learning algorithms to track behavior, we can delineate how these signals are transmitted to the pontine micturition control center (Barrington’s nucleus) to ultimately control urination. Together, this work will map interoceptive responses from the periphery all the way through the central control centers in the brain, and provide us with a roadmap to understand how the brain senses and commands the body.