A major CNS component of CNS control of gastrointestinal (GI) function, specifically CNS control of vagal outflow from the brain is the dorsal motor nucleus of the vagus (DMV). This nucleus contains perikarya of vagal efferent neurons that project to the esophagus, stomach and cecum, and to other organs such as the liver, pancreas and heart. Afferent inputs to this nucleus originate from peripheral sites such as specific areas of the GI tract (stomach, cecum) as well as specific sites in the brain (e.g., nucleus tractus solitaires, nucleus raphe obscurus). To understand how the CNS controls GI function, it is important to first understand how information processing occur in CNS centers such as the DMV. To understand, specifically, information processing in the DMV, it is essential to know the electrophysiological behavior of the DMV motoneurons (which is determined by the presence and distribution of different ionic currents in each neuron), and how the electrophysiological properties of DMV neurons are influenced by the neuroactive substance impinging upon them. Our hypothesis is that DMV is not a diffuse neuronal system that conveys information simultaneously to vast areas of the body (i.e., to the GI tract, liver, pancreas, and heart), but is highly organized neuronal system that conveys specific topographic types of information to targeted areas in the body. The experimental strategy for testing this hypothesis will be use the in vitro rat brain slice preparation and perform whole cell patch-clamp recording of single DMV neurons. With this preparation our specific aims are to: (1) determine whether all DMV neurons are homogenous in terms of their membrane currents, or does a heterogeneity in membrane currents exist that can be related to where DMV neurons project; (2) determine whether all DMV neurons respond in a uniform fashion to putative neurotransmitter thought to control DMV neurons, or is there a heterogeneity of responses of DMV neurons to a specific putative neurotransmitter that can be related to where the DMV neurons projects in the periphery; (3) determine whether stimulation of specific afferent inputs to DMV neurons such as inputs from the nucleus tractus solitaires (e.g. commissural part of the nucleus of the tractus solitaires which contains the A2 catecholaminergic cell group) and the nucleus raphe obscurus engage only a specific population of DMV neurons thus affecting a targeted area of the G.I. tract; and (4) confirm findings obtained using the in vitro brain slice preparation in an iv vivo preparation. Data obtained from pursing these four specific aim will reveal the neuronal currents that exist in DMV neurons, and how these currents are affected by neurotransmitter of brain and peripheral input to DMV neurons. Furthermore, we will have increased our understanding of how interplay between neuronal currents in DMV motoneurons and neurotransmitter released by afferent inputs can result in the pattern of neural activity that is sent to specific sites in the GI tract and to other visceral organs such as the liver, pancreas and heart.
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