The long-term goal of this research is to determine the neural mechanisms that produce vomiting, a potentially serious problem associated with motion, space, radiation and pregnancy sickness, treatment of cancer patients, and AIDS.. The present emphasis is to investigate the neural control of the major respiratory (diaphragm, intercostal, abdominal) muscles that generate the intra-abdominal and -thoracic pressure changes responsible for vomiting. Increased understanding of the neural circuitry that produces vomiting, together with a growing knowledge of multiple neurotransmitter receptor subtypes, should lead to improved pharmacological countermeasures for vomiting as well as possibly other respiratory-related dysfunctions. Most experiments will involve the use of """"""""fictive vomiting"""""""", which is characterized by bursts of coactivation of phrenic and abdominal motor nerves in decerebrate, paralyzed cats. The role of the following brain stem regions in (fictive) vomiting will be investigated by recording their single cell activity: (a) midline (raphe) neurons that may participate in control of phrenic and intercostal motoneurons and upper cervical inspiratory propriospinal neurons, (b) rostral ventral respiratory group (VRG) propriobulbar neurons that may inhibit bulbospinal inspiratory neurons and caudal VRG expiratory neurons, (c) caudal VRG expiratory neurons that may project to the nucleus of Onuf and be important for control of external urethral and anal sphincters, and (d) area postrema neurons that are thought to serve as a central chemoreceptor trigger zone for vomiting. The projection sites of brain stem neurons will be determined by antidromic activation of their axons. To anticipate the pattern of descending brain stem drives during fictive vomiting, a determination will be made of membrane potential changes occurring in phrenic, abdominal and intercostal motoneurons, including the role of inhibitory inputs in shaping motoneuronal discharge. As a prerequisite to intracellular recording from abdominal motoneurons, the activity of individual abdominal muscles will be determined during vomiting and, for comparison, other expulsive behaviors (coughing, sneezing). Finally, lesion experiments will be performed to delineate brain stem and upper cervical areas necessary for respiratory muscle activation during (fictive) vomiting, to determine regions not essential, and obtain information concerning the existence and location of an anatomically well-defined """"""""vomiting center"""""""".
