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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003732-16
Application #
8610910
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Platt, Christopher
Project Start
1998-05-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
16
Fiscal Year
2014
Total Cost
$356,058
Indirect Cost
$121,036
Name
University of Pittsburgh
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Sugiyama, Yoichiro; Suzuki, Takeshi; DeStefino, Vincent J et al. (2011) Integrative responses of neurons in nucleus tractus solitarius to visceral afferent stimulation and vestibular stimulation in vertical planes. Am J Physiol Regul Integr Comp Physiol 301:R1380-90

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