Vomiting is a consequence of a stereotyped pattern of co-contractions of the diaphragm and abdominal muscles that generate high intragastric pressures. The goal of this application is to decipher the processing of vestibular inputs by the medullary circuitry that produces vomiting, and to determine how this signal processing is affected by other inputs that can elicit emesis.
Specific Aim 1 will map the locations of neurons activated during vomiting and accompanying nausea elicited by stimulation of vestibular receptors and compare the sites to those activated during emesis triggered by gastrointestinal (GI) inputs.
Specific Aim 2 will employ inactivation of subregions of the vestibular nuclei (VN) to identify the area that is essential for producing vestibular-elicited vomiting. Once the brainstem regions containing neurons that participate in generating vomiting are established, subsequent experiments will ascertain the responses of cells in these areas to natural vestibular stimulation added to activation of GI receptors.
Specific Aim 3 will consider neuronal responses in nucleus tractus solitarius (NTS) and the VN, which respectively receive GI and labyrinthine inputs from the periphery that can induce emesis and nausea.
Specific Aim 4 A will determine the responses of neurons in a region that is a component of the vomiting pattern generator: the dorsal medullary lateral tegmental field (LTF) positioned between NTS and the retrofacial nucleus.
Specific Aim 4 B will consider the processing of signals by PBN, which is involved in transmitting viscerosensory signals to the forebrain, to provide insights into how integration of vestibular and visceral inputs together differs in this region critical for generating nausea and medullary elements that produce vomiting. At the conclusion of Aim 4 we will have thoroughly sampled the responses of neurons to labyrinthine stimulation in the major brainstem areas known to participate in triggering and coordinating vomiting and accompanying affective responses. We will also systematically determine how vestibular signals are transformed in the emetic circuit as they are relayed from the VN to NTS and finally to LTF and the PBN. Furthermore, we will ascertain how the presence of other emetic signals affects the processing of labyrinthine inputs, and whether this processing is profoundly altered immediately before or after an episode of vomiting. As such, the studies will provide insights into the signal integration responsible for the generation of motion sickness.

Public Health Relevance

Vomiting is highly significant and common clinical problem. Nausea and vomiting can occur during poisoning, cancer chemotherapy, recovery from anesthesia, activities in virtual environments (including civilian and military training simulators), and travel in cars, airplanes, and spacecraft. Motion sickness is the most common malady linked with the vestibular system, but the processing of vestibular signals by the brainstem neurons that trigger and coordinate emesis is poorly understood. The proposed experiments comprise the first systematic study of how vestibular signals are transformed by the neural pathways that trigger and coordinate vomiting and will also ascertain how inputs from the viscera affect this processing;as such, the work will provide fundamental new insights into the mechanisms that generate vomiting.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Sensorimotor Integration Study Section (SMI)
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Platt, Christopher
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University of Pittsburgh
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Balaban, Carey D; Yates, Bill J (2017) What is nausea? A historical analysis of changing views. Auton Neurosci 202:5-17
McCall, Andrew A; Miller, Daniel J; Catanzaro, Michael F et al. (2015) Hindlimb movement modulates the activity of rostral fastigial nucleus neurons that process vestibular input. Exp Brain Res 233:2411-9
Catanzaro, Michael F; Miller, Daniel J; Cotter, Lucy A et al. (2014) Integration of vestibular and gastrointestinal inputs by cerebellar fastigial nucleus neurons: multisensory influences on motion sickness. Exp Brain Res 232:2581-9
Horn, Charles C; Meyers, Kelly; Lim, Audrey et al. (2014) Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews. Am J Physiol Regul Integr Comp Physiol 306:R341-51
Yates, Bill J; Catanzaro, Michael F; Miller, Daniel J et al. (2014) Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness. Exp Brain Res 232:2455-69
Yates, Bill J; Bolton, Philip S; Macefield, Vaughan G (2014) Vestibulo-sympathetic responses. Compr Physiol 4:851-87
Balaban, Carey D; Ogburn, Sarah W; Warshafsky, Susan G et al. (2014) Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation. PLoS One 9:e86730
McCall, Andrew A; Moy, Jennifer D; Puterbaugh, Sonya R et al. (2013) Responses of vestibular nucleus neurons to inputs from the hindlimb are enhanced following a bilateral labyrinthectomy. J Appl Physiol (1985) 114:742-51
Arshian, Milad S; Puterbaugh, Sonya R; Miller, Daniel J et al. (2013) Effects of visceral inputs on the processing of labyrinthine signals by the inferior and caudal medial vestibular nuclei: ramifications for the production of motion sickness. Exp Brain Res 228:353-63
McCall, Andrew A; Moy, Jennifer D; DeMayo, William M et al. (2013) Processing of vestibular inputs by the medullary lateral tegmental field of conscious cats: implications for generation of motion sickness. Exp Brain Res 225:349-59

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