We know almost nothing about the neural basis of the Brain-Body connection. This connection is the circuitry that enables motor, cognitive and affective processing to have a major impact on the function of internal organs such as the stomach, heart and spleen. Inappropriate signals in these networks are thought to contribute to the generation of some prevalent medical illnesses, and to cause the so-called "functional" and psychosomatic disorders. The experiments proposed in this application will fill a major gap in our knowledge. We will identify the cortical areas that influence, and in some instances control the function of the gastrointestinal (GI), cardiovascular and immune systems. The brain-body connection is based on chains of synaptically-connected neurons. No conventional neuroanatomical tracer is capable of revealing multi-synaptic circuits. To overcome this shortcoming, we developed the use of rabies virus as a transneuronal tracer in non-human primates. We propose to use this unique approach to reveal the complex networks that are responsible for the top-down influence of the central nervous system on the stomach, heart and spleen. There is a growing awareness that many medical symptoms, especially those without identifiable pathology, may be caused by a disturbance in the brain-body connection. This is especially the case for often intractable disorders such as irritable bowel syndrome, stress- and depression-related heart disease, and fibromyalgia. Thus, the information that will come from our studies has the potential to transform the way we view and treat these disorders. In essence, the brain-body connection is a construct that lacks a concrete basic science foundation. The results from the proposed research will establish a structural framework for the brain-body connection and thus, create new opportunities for rigorous research and novel approaches for treatment. This information, because of its all-encompassing nature, will be of interest to many, if not all of the NIH Institutes and Centers.