Autonomic (motor) and sensory nerves regulate healthy function of muscle, vascular, glandular and immune tissues in the urogenital system, and participate in responses to infection, inflammation and pain. The complex structure of these neural pathways located between the spinal cord and the urogenital organs underlies their vulnerability to injury during pelvic surgery. This complexity also provides a major technical challenge to visualize and interpret structure. Our goal is to map the structure and connections of these urogenital neural circuits from the macroscopic to microscopic scale, to inform models of nerve-organ regulation and support the development of new bioelectronic therapeutic approaches (neuromodulation).
This presentation will first summarise general principles of the neural regulation of urogenital organs and examples of known or potential neural contributors to clinical conditions. Most of the presentation will then focus on the technical approaches we have applied to visualise and map these neural pathways, in experimental rodents and humans. While elements of neural and vascular networks can be assessed in conventional tissue sections (2D), much more can be learned about these networks in 3D within intact organs. We have applied the iDISCO tissue clearing method to make samples completely transparent, in combination with immunofluorescence and light sheet fluorescence microscopy. This has enabled us to build maps of neural and vascular networks in entire organs from adult rodents and large samples of organs and neural plexus from human organ donors. I will also present data from rodent studies where we have used a specific adeno-associated virus to identify mechanosensory axons in the urogenital system and microsurgical nerve tracing studies to identify spinal cord circuits specifically involved in urogenital functions. Together, these data provide new biological insights into urogenital organ structure, its neural and vascular networks and technical solutions to probe mechanisms contributing to clinical conditions.