# Neurotransmission in tastebuds

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $463,724

## Abstract

PROJECT SUMMARY
Type III “presynaptic” taste cells respond to sour and some salty stimuli with action potentials and release
neurotransmitter at conventional synapses with afferent nerve fibers. The identity of the transmitters involved,
however, is still unclear. We have shown previously that all taste stimuli (including sour and salty) require ATP
signaling to neural P2X receptors for transmission to afferent fibers. Nonetheless, ATP release from Type III
cells has not been detected. Conversely, Type III cells do release serotonin (5-HT) which activates 5-HT3
receptors on afferent nerve fibers but neither knockout nor pharmacological inhibition of 5-HT3 completely
eliminates responses to acids or salts, suggesting other neurotransmitters are involved. One problem in
studying transmission from Type III cells is that the conventional stimuli used to activate these cells -- acids,
salts, and KCl -- all have non-specific effects on other cell types in the taste bud. To circumvent this problem,
we employ an optogenetic strategy permitting direct stimulation of Type III cells with light rather than
chemicals. We developed a mouse that expresses Cre recombinase selectively in type III taste cells relying on
Pkd2l1 as a Cre driver. When these Pkd2l1-Cre mice are crossed with “floxed” channelrhodopsin (ChR2) mice
ChR2 is faithfully expressed in taste cells immunoreactive for PKD2L1 with no off-target expression in other
taste cell types. Flashing 470 nm light onto the tongue elicits responses in the chorda tympani and
glossopharyngeal nerves that are robust and repeatable, resembling responses to sour and salty stimuli. In
this proposal we will utilize these Pkd2l1-ChR2 mice plus other gene-targeted mice to investigate the
neurotransmitters that are used by these cells to communicate with the nervous system, and the perceptual
qualities evoked by selective stimulation of PKD2l1 Type III cells. Aim 1 will investigate the role of ATP and
other neurotransmitters (i.e., 5-HT, GABA, and NE) in activating geniculate ganglion neurons that selectively
innervate Type III cells. Calcium imaging of isolated geniculate ganglion cells will identify transmitters that
activate these neurons, and chorda tympani and glossopharyngeal nerve responses to light in the Pkd2l1-
ChR2 mice will allow us to test the role of their cognate receptors in vivo. Aim 2 will address the perceptual
quality elicited by stimulation of Pkd2l1-ChR2 cells, using behavioral paradigms, and cFos activation will be
used to address the central representation of PKD2L1-expressing Type III cells. In Aim 3 we will test the
hypothesis that PKD2L1-Type III cells participate in an intragemmal (intra taste bud) circuit, resulting in
modulation of other taste qualities, particularly those transduced by Type II cells. Results from these studies
will provide important new information about transduction, afferent neurotransmission, and intragemmal
signaling in Type III taste cells.

## Key facts

- **NIH application ID:** 9948626
- **Project number:** 5R01DC012555-09
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Sue C. Kinnamon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $463,724
- **Award type:** 5
- **Project period:** 2012-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948626

## Citation

> US National Institutes of Health, RePORTER application 9948626, Neurotransmission in tastebuds (5R01DC012555-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948626. Licensed CC0.

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