This is an application for a First Independent Research Support and Transition (FIRST) Award which is to replace a currently funded New Investigator Research Award after the first year of support. The underlying physiological mechanisms which alter motility during enteric parasitism are unknown. The long-term objective of this project is to elucidate the role of the enteric nervous system in the onset and maintenance of alterations of intestinal motor patterns during enteric parasitic infection.
The specific aim i s to characterize the effects of parasitic infection on the physiology of the enteric nervous system of guinea pigs infected with the helminth, Trichinella spiralis. The rationale is that alterations of gut motility during parasitism are mediated through inflammatory and immunological reactions which transduce signals through neural pathways in the enteric nerve plexuses which coordinate activity of the intestinal musculature. The effects of parasitic infection on enteric nervous system function will be assessed by direct intracellular electrophysiological recording techniques. These methods will be used to examine: (1) the electrical behavior and synaptic circuitry of neurons from enteric ganglia of small intestine of nonimmune and immune animals during infection with T. spiralis; (2) changes in chemical neurotransmission during infection by assessing responsiveness to exogenously applied neurotransmitters, neuropeptides, and chemical mediators of inflammation and allergy; (3) the effects of application of parasites and parasite antigens to an intact mucosa-nerve preparation in order to establish a connection between the process of parasite establishment and the induction of inflammation and immunological responsiveness in the gut with altered enteric nervous system function; (4) the effects of passive transfer of serum from immune to non-immune hosts to establish the immunological basis of altered enteric neural function; (5) identification of specific chemical mediators released and involved in altered enteric neural function in immune hosts. This approach will provide more definitive information on the physiological mechanisms responsible for intestinal motor disturbances during enteric parasitism, and these studies will be the first to address the interactions between the nervous and immune systems in terms of integrative function.
