The central nervous system strongly influences gastric functions of acid secretion and motility, and plays a major role in many pathologic processes such as peptic ulcer disease, motility and eating disorders. Neuropeptides have an important role in how the brain modulates vagauy mediated functions, and may be involved in disease processes. Thyrotropin-releasing homione (TRH) and bombesin are two important neuropeptides influencing brain control of gastric function, with opposing actions on gastric secretion and motility when microinjected into the dorsal vagal complex (DVC). While physiologic responses to these two neuropeptides have been extensively studied, the anatomic basis of these responses remains poorly defined. The overall goal of this proposal is to better understand the origin, connectivity and terminal ultrastructure of TRH and bombesin containing neurons in the brain that influence the DVC in rats. First, the topographic organization of TRH-immunoreactive (IR) neurons and the location of bombesin-IR neurons projecting to the DVC wig be defined by combining retrograde neuronal tracing with immunohistochemistry. Second, the ultrastructure of bombesin terminals in the DVC will be studied using electron microscopy to determine the types of bombesin-IR synaptic structures present, their location, and their relationship to gastric motoneurons and TRH-IR nerve terminals. Third, neurons in central nervous system nuclei that innervate gastric vagal motoneurons will be mapped using pseudorabies virus, a new neuroanatomical tracer that crosses synapses. This tracer will be combined with immunohistochemistry to determine which TRH- and bombesin-IR neurons have direct connections with gastric vagal motoneurons. Fourth, the connectivity of divergent axon collaterals of TRH-IR raphe neurons will be defined by combining double retrograde tracing with immunohistochemistry.
