The presence of acidic substances in the mouth evokes a sensation of sour taste. But oropharyngeal acidification is not only attributable to ingested substances, but may be produced by gastric reflux which evokes strong respiratory and salivary reflexes as well as a sensation of disgust. Acidic substances in the oral cavity not only trigger the taste system but also activate pH-sensitive general mucosal nerve fibers. Previous studies have identified the subset of taste cells necessary for sour transduction, but how these cells transmit the information to the gustatory nerves and thence the brainstem gustatory relay nuclei remains unclear. Acid-responsive mucosal nerve fibers also transmit information about intraoral pH and end within the brainstem in a partially overlapping fashion with the sour taste fibers. Experiments in this proposal utilize behavioral, pharmacological, anatomical and physiological means to examine to what degree the sour taste and non- taste systems contribute to the detection and avoidance of acids. The experiments rely on unique knockout rodent models to dissociate the functions and roles of the two intraoral acid-responsive systems. We will use both pharmacological and genetic tools to study what areas of the brainstem are activated by stimulation of one system in the absence of the other.

Public Health Relevance

The sense of taste evolved to allow discrimination of nutritionally important compounds from toxic substances. The off-taste of a medicine can be a limiting factor in patient compliance. In addition, acid reflux evokes strong aversive respiratory and salivary reflexes due to the presence of acid in the oropharynx. A better understanding of the mechanisms used by oral acid sensors to detect noxious chemicals and transmit chemosensory information to the nervous system may lead to the development of pharmaceuticals that can limit the bad tastes of many drugs and ameliorate the negative hedonic aspects of reflux disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC012931-01A1
Application #
8574596
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2013-07-01
Project End
2018-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$328,313
Indirect Cost
$115,813
Name
University of Colorado Denver
Department
Biology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Stratford, J M; Larson, E D; Yang, R et al. (2017) 5-HT3A -driven green fluorescent protein delineates gustatory fibers innervating sour-responsive taste cells: A labeled line for sour taste? J Comp Neurol 525:2358-2375
Stratford, Jennifer M; Thompson, John A; Finger, Thomas E (2017) Immunocytochemical organization and sour taste activation in the rostral nucleus of the solitary tract of mice. J Comp Neurol 525:271-290
Stratford, Jennifer M; Thompson, John A (2016) MSG-Evoked c-Fos Activity in the Nucleus of the Solitary Tract Is Dependent upon Fluid Delivery and Stimulation Parameters. Chem Senses 41:211-20
Gaillard, Dany; Stratford, Jennifer M (2016) Measurement of Behavioral Taste Responses in Mice: Two-Bottle Preference, Lickometer, and Conditioned Taste-Aversion Tests. Curr Protoc Mouse Biol 6:380-407
Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja et al. (2015) The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves. J Neurosci 35:15984-95
Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B et al. (2015) Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice. J Physiol 593:1113-25
Stratford, Jennifer M; Thompson, John A (2014) Beta-galactosidase staining in the nucleus of the solitary tract of Fos-Tau-LacZ mice is unaffected by monosodium glutamate taste stimulation. PLoS One 9:e107238