The taste system is capable of remarkable plasticity following denervation of taste receptor cells. Environmental influences at the time of nerve section play an important role in this functional plasticity. Adult rats placed on a sodium-restricted diet soon after sectioning of the chorda tympani (CT) nerve, which innervates taste receptor cells, exhibit long-lasting deficits in neurophysiological taste responses. Surprisingly, intact taste receptors also demonstrate altered taste responses within days after contralateral denervation. In fact, up-regulation of immune activity in sodium-deficient rats leads to recovery of normal taste responses in the intact CT nerve. This novel interaction between sensory and immune function was unexpected, and little is currently known about the role of the immune system in the normal or degenerating taste system. The site of changes in taste function after denervation is the amiloride-sensitive sodium channel, or ENaC, on taste receptor cells. Our long-term goal is to determine the mechanisms by which the immune system modulates ENaC function. In the current proposal, immune cells that potentially affect taste function during degeneration must first be identified. Leukocyte subtypes will be identified, counted, and their spatial relationship to denervated and intact taste buds mapped over time post-sectioning. The expression of adhesion molecules an essential signal for leukocyte entry to tissue, will be examined after denervation of taste receptor cells. Leukocyte proliferation and activation initiated by unilateral denervation of taste receptor cells will also be investigated. We hypothesize that each of these measures of immune activity is up-regulated after CT sectioning in control-fed but not sodium-restricted rats. Indeed, there is evidence that dietary sodium restriction is immunosuppressive. Finally, specific populations of leukocytes will be depleted, and the functional consequences for the degenerating taste system assessed neurophysiologically. ENaC expression will also be examined after leukocyte depletion, to determine if leukocyte regulation of the channel is a mechanism for altered sodium transduction in taste receptor cells. These experiments will provide powerful evidence for the influence of specific leukocyte populations on taste function in vivo. Proposed studies are also important for our understanding of functional interactions between neurons, sensory receptor cells, and leukocytes, and of neural plasticity after injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC005811-01A1
Application #
6684569
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Davis, Barry
Project Start
2003-07-01
Project End
2008-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$286,000
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Physiology
Type
Schools of Medicine
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912
He, Lianying; McCluskey, Lynnette Phillips (2018) Regression of Lingual Lymphatic Vessels in Sodium-restricted Mice. J Histochem Cytochem 66:377-384
Kumarhia, Devaki; He, Lianying; McCluskey, Lynnette Phillips (2016) Inflammatory stimuli acutely modulate peripheral taste function. J Neurophysiol 115:2964-75
Zhu, X; He, L; McCluskey, L P (2014) Ingestion of bacterial lipopolysaccharide inhibits peripheral taste responses to sucrose in mice. Neuroscience 258:47-61
Feng, J; Bendiske, J; Morest, D K (2012) Degeneration in the ventral cochlear nucleus after severe noise damage in mice. J Neurosci Res 90:831-41
He, L; Yadgarov, A; Sharif, S et al. (2012) Aging profoundly delays functional recovery from gustatory nerve injury. Neuroscience 209:208-18
Shi, Liqiao; He, Lianying; Sarvepalli, Padma et al. (2012) Functional role for interleukin-1 in the injured peripheral taste system. J Neurosci Res 90:816-30
Steen, P W; Shi, L; He, L et al. (2010) Neutrophil responses to injury or inflammation impair peripheral gustatory function. Neuroscience 167:894-908
Guagliardo, Nick A; West, Katie Nicole; McCluskey, Lynnette P et al. (2009) Attenuation of peripheral salt taste responses and local immune function contralateral to gustatory nerve injury: effects of aldosterone. Am J Physiol Regul Integr Comp Physiol 297:R1103-10
Wall, Pamela Lea; McCluskey, Lynnette Phillips (2008) Rapid changes in gustatory function induced by contralateral nerve injury and sodium depletion. Chem Senses 33:125-35
Cavallin, Melissa Ann; McCluskey, Lynnette Phillips (2007) Upregulation of the chemokine monocyte chemoattractant protein-1 following unilateral nerve injury in the peripheral taste system. Neurosci Lett 413:187-90

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