NEUROPHYSIOLOGICAL STUDIES OF VOMITING

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The long-term goal is to determine the neural mechanisms that produce vomiting, a potentially serious problem commonly associated with motion and radiation sickness, treatment of cancer patients, and acquired immune deficiency syndrome (AIDS). Initial studies will investigate the control of the major respiratory muscles (abdominal and diaphragm) that produce the pressure changes responsible for vomiting, with the longer term objective of determining how this neural circuitry is engaged when vomiting is produced during various conditions. We will record from a variety of single brain stem neurons during "fictive vomiting" in decerebrate, paralyzed cats in order to investigate the possible role of various cell groups in the control of these respiratory muscles during vomiting. Fictive vomiting is defined by a characteristic pattern of co-activation of phrenic and abdominal muscle nerves, elicited in response to emetic agents, that would be expected to produce vomiting in unparalyzed animals. Cells that will be studied include descending inspiratory neurons in the dorsal and ventral medullary respiratory groups (DRG, VRG) and in the upper cervical spinal cord (Cl-C2), caudally projecting expiratory neurons in the Botzinger complex of the rostral VRG, and neurons in the raphe obscurus nucleus (which produce phrenic nerve excitation) and dorsal-lateral reticular formation (which has been suggested by others to contain a "vomiting center"). The abdominal muscles have been shown to remain active during vomiting after removal of excitatory input from expiratory neurons in the caudal VRG. The possible contribution of spinal reflexes to abdominal muscle activation during vomiting will be examined in decerebrate cats by comparing abdominal activity after cutting selected spinal dorsal roots (eliminating spinal afferent inputs or after spinal section at T1-2 (eliminating descending inputs). The effects of cutting the axons of caudal VRG expiratory neurons on abdominal nerve activity will also be determined during fictive vomiting (i.e., in a preparation in which spinal stretch reflexes would not be elicited). A series of lesion experiments will also be carried out to better delineate the brain stem regions that are necessary for normal activation of the major respiratory muscles during (fictive) vomiting. Better understanding of the pathways that produce vomiting should lead to more effective pharmaceutical countermeasures.