Taste receptor cells detect chemicals in our food and communicate this information to the nerve fibers innervating them. Our goal is to understand the structural and functional relationship between taste receptor cells and innervating neurons. Because taste receptor cells undergo continuous renewal and must constantly attract and connect to nerve fibers even in the adult, some mechanism exists to control this process. Since the neurotrophin BDNF controls initial innervation of taste buds and is present in adult taste receptor cells, it may have this role. BDNF also can function as a neuromodulator regulating function, so it is certainly possible that BDNF can regulate both innervation and/or function of adult taste buds. Here we are testing the hypothesis that BDNF signaling through its receptor, TrkB, regulates both the structural and functional connections between taste receptor cells and ganglion neurons. The proposed studies combine sparse cell genetic labeling with 3-dimensional analysis of the taste bud and electrophysiology, in mice where TrkB-signaling can be blocked using a combination of chemical and genetic approaches to: 1) determine the identity and connectivity of BDNF expressing taste receptor cells, 2) determine the role of BDNF-TrkB-signaling in maintaining this connectivity, and 3) determine if BDNF-TrkB signaling regulates taste function. Together, these experiments will determine how specific taste receptor cells (BDNF-expressing) become innervated by a subset of taste ganglion neurons (TrkB-expressing) during taste cell renewal and will determine if BDNF-TrkB-signaling is an important gustatory system neuromodulator of this pathway.

Public Health Relevance

Taste disorders can have detrimental effects on a person's health and quality of life. The underlying mechanisms of these disorders are not understood, but could result from disruption of the connections between taste buds and the neurons carrying taste information to the brain. Here we are looking at the role of neurotrophins in maintaining these connections and evaluating the effects of potentially therapeutic neurotrophin agonists and antagonists on taste function, with an eye toward basic research applicable to the larger clinical question of nerve regeneration in adulthood.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC007176-13
Application #
9313218
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sullivan, Susan L
Project Start
2005-03-01
Project End
2021-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
13
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Louisville
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Sun, Chengsan; Krimm, Robin; Hill, David L (2018) Maintenance of Mouse Gustatory Terminal Field Organization is Dependent on BDNF at Adulthood. J Neurosci :
Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin (2017) Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers. Mol Cell Neurosci 82:195-203
Ohman-Gault, Lisa; Huang, Tao; Krimm, Robin (2017) The transcription factor Phox2b distinguishes between oral and non-oral sensory neurons in the geniculate ganglion. J Comp Neurol 525:3935-3950
Meng, Lingbin; Huang, Tao; Sun, Chengsan et al. (2017) BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section. Exp Neurol 293:27-42
Biggs, Bradley T; Tang, Tao; Krimm, Robin F (2016) Insulin-Like Growth Factors Are Expressed in the Taste System, but Do Not Maintain Adult Taste Buds. PLoS One 11:e0148315
Meng, Lingbin; Ohman-Gault, Lisa; Ma, Liqun et al. (2015) Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds. eNeuro 2:
Sun, Chengsan; Dayal, Arjun; Hill, David L (2015) Expanded terminal fields of gustatory nerves accompany embryonic BDNF overexpression in mouse oral epithelia. J Neurosci 35:409-21
Huang, Tao; Ma, Liqun; Krimm, Robin F (2015) Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation. Dev Biol 405:225-36
Huang, Tao; Krimm, Robin F (2014) BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol 386:308-20
Patel, Ami V; Krimm, Robin F (2012) Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor. Dev Biol 365:50-60

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