A key question in taste is how the system maintains a stable message about taste quality while receptor cells are turning over, constantly changing connections between the taste bud and its nerve fibers. To accomplish this the taste periphery must employ a high degree of receptoneural plasticity. We are beginning to understand the neurochemical basis of receptoneural plasticity in relation to the precision with which ganglion cells are connected to taste buds. Plasticity is most dramatic in the degeneration of taste buds when denervated, and their rapid regeneration when reinnervated. Evidence is growing that such neuron-target cell plasticity involves neurotrophins and their tyrosine kinase receptors. In hamster, the fungiform buds of which uniquely resist degeneration after denervation, we identified enrichments in BDNF, TrkB and TrkC not seen in vallate or foliate buds that do not resist denervation, e.g., neurotrophin-positive fungiform bud cells are uniquely unaffected by denervation. Conceivably, cells expressing these growth factors are involved in taste bud maintenance and in promoting nerve fiber in-growth. The possibilities that such maintenance involves increases in gemmal cell genesis to offset cell losses due to denervation, or influences on cell lifespan, will be evaluated by BrdU labeling. A role for neurotrophins in the targeting of nerve fibers will be explored with multicolored lipophilic dyes to demonstrate precisely the connectivity between small populations of ganglion cells and a single buds. Studies of taste bud neurotrophin expression in relation to denervation, reinnervation, gemmal cell genesis, and innervation patterns will emphasize analysis of the mouse. Mouse fungiform buds have uniquely discrete innervation patterns and express neurotrophins differently (e.g., less BDNF) than hamster buds. Species comparison allows formulation of hypotheses about the role of neurotrophins and receptors in taste bud maintenance and innervation. An existing BDNF epithelial overexpressing mouse line will be used to test the hypothesis that increased peri-bud neurotrophin results in denser, less discrete innervation and heightened bud cell genesis or lifespan. For comparison, bud-specific BDNF knockout mice will be generated to specifically test the effect of bud neurotrophin absence on innervation, reinnervation and gemmal cell differentiation. Additionally, an inducible BDNF bud knockout mouse will be generated to test the effect of BDNF loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001901-08
Application #
6908082
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Davis, Barry
Project Start
1993-04-01
Project End
2009-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
8
Fiscal Year
2005
Total Cost
$276,640
Indirect Cost
Name
University of California San Diego
Department
Surgery
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Ganchrow, Donald; Ganchrow, Judith R; Cicchini, Vanessa et al. (2014) Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections. J Comp Neurol 522:1565-96
Zaidi, Faisal N; Todd, Krista; Enquist, Lynn et al. (2008) Types of taste circuits synaptically linked to a few geniculate ganglion neurons. J Comp Neurol 511:753-72
Ganchrow, Donald; Ganchrow, Judith R; Verdin-Alcazar, Mary et al. (2003) Brain-derived neurotrophic factor-, neurotrophin-3-, and tyrosine kinase receptor-like immunoreactivity in lingual taste bud fields of mature hamster. J Comp Neurol 455:11-24
Ganchrow, Donald; Ganchrow, Judith R; Verdin-Alcazar, Mary et al. (2003) Brain-derived neurotrophic factor-, neurotrophin-3-, and tyrosine kinase receptor-like immunoreactivity in lingual taste bud fields of mature hamster after sensory denervation. J Comp Neurol 455:25-39
Whitehead, M C; McGlathery, S T; Manion, B G (1995) Transganglionic degeneration in the gustatory system consequent to chorda tympani damage. Exp Neurol 132:239-50