Publication Date

2012-03-06

Availability

Embargoed

Embargo Period

2013-03-06

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Neuroscience (Medicine)

Date of Defense

2012-02-13

First Committee Member

Nirupa Chaudhari

Second Committee Member

Robert W. Keane

Third Committee Member

Gerhard Dahl

Fourth Committee Member

Jeffrey L. Goldberg

Fifth Committee Member

Susan Travers

Abstract

Taste is detected by cells of taste buds in the oral cavity. Mammalian taste buds contain three types of cells: receptor, presynaptic, and glial-like. Of these three, glial-like cells are the least studied. Their only known function is that they clear neurotransmitters from the extracellular space. The present work describes two previously undocumented properties of glial-like cells. First, Oxytocin receptor (OXTR) mRNA was detected by RT-PCR in taste tissue of mice. In the taste buds of Oxtr-YFP knockin mice, YFP was seen in glial-like taste cells and other cells immediately outside the taste bud, but no other cells in oral epithelium. Oxytocin (OXT) elicited Ca2+ responses from cells that resemble glial-like taste cells (by criteria including gene expression and lack of excitability). The EC50 for OXT in these cells was 33 nM, and responses saturated at 1 µM. 500 nM L-371,257 (an OXTR antagonist) significantly inhihited the responses to OXT. In a semi-intact preparation of lingual slices, OXT did not alter bitter tastant-evoked Ca2+ responses. Further, in behavioral studies, OXT (10 mg/kg i.p.) did not alter the responses of mice to aversive salty (NaCl), bitter (quinine), or sour (citric acid) solutions. In contrast, OXT (0.1 mg/kg i.p.) significantly decreased taste behavioral responses to low-to-intermediate concentrations of sucrose. My data suggest that OXT may modulate sweet taste sensitivity in vivo by acting on glial-like cells in taste buds. Second, Renal Outer Medullary K channel (ROMK) mRNA was also detected by RT-PCR in taste buds . Immunostaining revealed that ROMK is localized to the apical tips of glial-like taste cells. In the kidney, ROMK, apically localized in nephron epithelium facilitates a unidirectional flow (i.e. excretion) of K+. I suggest that, analogous to glia in the central nervous system, glial-like taste cells homeostatically redistribute extracellular [K+ ] within taste buds to maintain their sensitivity. The results of this study reveal that glial-like taste cells resemble nervous system glia in more ways than simply clearing neurotransmitters. They may also modulate the sensory output of the taste bud and buffer the extracellular [K+]. A more active role for glial-like cells in the functioning of the taste bud should be investigated.

Keywords

taste; glia; appetite; feeding; hormone; oxytocin

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