The understanding of olfactory transduction, the process used by olfactory neurons to recognize and assess the concentration of volatile odorant molecules is the ultimate goal of this project. It is clear that for a substantial number of odorants olfactory transduction takes place through receptor-mediated activation of G-proteins leading to formation of the second messenger adenosine- 3', 5'-monophosphate (cAMP). The subsequent elevation in intracilliary cAMP concentration causes opening of cAMP-gated cation channels, influx of Ca/2+ and subsequent gating of Ca/2+-activated chloride channels that depolarize olfactory receptor neurons. Furthermore, there is also controversial evidence indicating that some odors may stimulate formation of inositol-1,4,5-triphosphate electing opening of InsP/3-gated non-specific cation channels which would also elicit cell depolarization. However, in invertebrates, amphibians and fish there is solid evidence for inhibitory pathways that elicit opening of K+ channels thereby causing cell hyperpolarization, and a decrease in the frequency of action potential firing. In this grant proposal we present preliminary evidence suggesting that odorants elicits inhibitory responses in mouse olfactory receptor neurons, and we propose to study the molecular mechanisms mediating inhibitory olfactory responses in mammals, including humans, using a multidisciplinary approach including biophysical and electrophysiological measurements. In addition, we propose to determine mechanism that mediates odor-induced decreases in intracellular calcium ([Ca/2+]/i) detected in a large fraction of human olfactory neurons, that cannot be explained within the context of the currently proposed models of olfactory transduction. These studies will lead to a better understanding of olfactory transduction in mammals, including humans. These results provide the basis for studies of the cellular and molecular etiology of olfactory dysfunction in humans.

Project Start
1998-04-01
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Finger, Thomas E; Bartel, Dianna L; Shultz, Nicole et al. (2017) 5HTR3A-driven GFP labels immature olfactory sensory neurons. J Comp Neurol 525:1743-1755
Tizzano, Marco; Finger, Thomas E (2013) Chemosensors in the nose: guardians of the airways. Physiology (Bethesda) 28:51-60
Finger, Thomas E (2009) Evolution of gustatory reflex systems in the brainstems of fishes. Integr Zool 4:53-63
Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E (2009) Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish: cellular organization and neurotransmitters. J Comp Neurol 516:213-25
Huesa, Gema; Ikenaga, Takanori; Bottger, Barbel et al. (2008) Calcium-fluxing glutamate receptors associated with primary gustatory afferent terminals in goldfish (Carassius auratus). J Comp Neurol 506:694-707
Finger, Thomas E (2008) Sorting food from stones: the vagal taste system in Goldfish, Carassius auratus. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 194:135-43
Yee, Cindy; Bartel, Dianna L; Finger, Thomas E (2005) Effects of glossopharyngeal nerve section on the expression of neurotrophins and their receptors in lingual taste buds of adult mice. J Comp Neurol 490:371-90
Linschoten, Miriam R; Harvey Jr, Lewis O (2004) Detecting malingerers by means of response-sequence analysis. Percept Psychophys 66:1190-201
Hall, Joshua M H; Bell, Melanie L; Finger, Thomas E (2003) Disruption of sonic hedgehog signaling alters growth and patterning of lingual taste papillae. Dev Biol 255:263-77
Finger, Thomas E; Bottger, Barbel; Hansen, Anne et al. (2003) Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci U S A 100:8981-6

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