The goal of my research is to understand how inflammation in the nervous system (neuroinflammation) leads to long-term changes in neural circuitry. Within this context, we focus on the regulation of neural networks by glial cells, with particular interests in clarifying the role of glial cells in nervous system physiology and elucidating how glial changes during neuroinflammation contribute to neurodegenerative diseases. We are addressing this issue by exploring how neuron-glia interactions in the enteric nervous system (ENS) regulate gut physiology and pathophysiology. The ENS is particularly well suited for this kind of work because neuron-glia interactions in the gut can be studied in situ using preparations with intact synaptic pathways or in vivo in animal models. Further, the synaptic pathways of enteric neural networks are well defined and the output of ENS activity can be clearly assessed with functional assays. Our experiments will allow us to understand the fundamental rules that govern cell to cell communication in the ENS and elucidate the molecular machinery that contributes to changes in enteric network output. This work is important because it will lead to an understanding of the basic mechanisms that underlie altered gut function in GI motility and functional bowel disorders. These are debilitating disorders that affect up to 25% of the U.S. population and account for over $30 billion/year in healthcare costs. I expect that the basic rules of neuron-glia interactions we uncover in our studies will be broadly applicable to the nervous system as a whole. Thus, I expect that my research will lead to the development of new therapies for a broad range of nervous system disorders.