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The neural representation of taste quality at the periphery

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Abstract

The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium1. To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator2 in central and peripheral neurons, and used a gradient refractive index microendoscope3 combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.

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Figure 1: Thy1-GCaMP3 transgenic mice express functional GCaMP3 in taste ganglion cells.
Figure 2: In vivo two-photon microendoscopy of the geniculate ganglion.
Figure 3: Selective responses of geniculate ganglion neurons.
Figure 4: Representation of taste in the primary sensory ganglia.

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Acknowledgements

We thank the National Institute of Dental and Craniofacial Research (NIDCR) transgenic-core and C. Guo at Janelia Farms for help in generating the Thy1-GCaMP3 mouse lines, B. Shields for histology support, and Y. Oka and M. Butnaru for nerve recording and pharmacological advice. We also thank members of the Zuker laboratory for helpful comments. This research was supported in part by the intramural research program of NIDCR (N.J.P.R.). C.S.Z. is an investigator of the Howard Hughes Medical Institute and a Senior Fellow at Janelia Farms.

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Contributions

R.P.J.B. designed the study, carried out the imaging experiments, analysed data and wrote the paper; S.G.-S. developed viral gene delivery to ganglion neurons and characterized the transgenic lines; J.C. characterized the transgenic lines, carried out initial imaging experiments and analysed data; D.A.Y. collected and analysed data; M.J.S. provided microendoscopy expertise; N.J.P.R. and C.S.Z. designed the study, analysed data and wrote the paper.

Corresponding authors

Correspondence to Nicholas J. P. Ryba or Charles S. Zuker.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Thy1–GCaMP3 mice show normal physiological responses to tastants.

a, Representative nerve recording traces from control and Thy1-GCaMP3 mice in response to various tastants (see Methods for details). b, Quantification of neural responses (mean + s.e.m.) show that Thy1-GCaMP3 mice (n = 4) are indistinguishable from wild-type mice (n = 3; Student’s t-test; NaCl, P = 0.85; bitter, P = 0.46; sour, P = 0.94; sweet, P = 0.69; umami, P = 0.77). Recordings were normalized to responses to KCl (500 mM). Horizontal bars below the traces mark the time and duration of the stimulus.

Extended Data Figure 2 Reproducibility of tastant-evoked responses in geniculate ganglion neurons.

a, Representative images of calcium-evoked GCaMP3 activity in response to sweet (left) and bitter (right) stimulation. Four relative fluorescence images are shown from separate trials. In each trial, the identical cell populations were activated. b, We tested 105 sweet responding cells and 168 bitter responding cells for their reproducibility in our automated scoring algorithm for four trials. The histograms show the number of times the cells respond all four times, three out of four, two out of four, and one out of four. c, Sample traces of four representative neurons challenged with 50 trials of the same tastant over a time window of 10 min. Note the high reliability in the activation of the neurons. This experiment also illustrates the desensitization of bitter neurons (bottom traces) over time. Horizontal bars below the traces mark the time and duration of the stimulus.

Extended Data Figure 3 Quantification of taste ganglion responses.

ad, Rank-ordered plot of calcium transient amplitudes for various singly tuned ganglion neurons (see text and Fig. 3). For each cell, the mean response amplitudes for preferred stimulus (red) and the mean amplitude of its next-strongest tastant response (grey) are shown; minor dots indicate individual trial amplitudes. e, Quantification of mean response amplitudes in singly tuned salt ganglion neurons before and after amiloride treatment (10 μM, n = 23 cells; paired t-test, P < 0.001). f, Quantification of mean response amplitudes in singly tuned bitter cells before and after AITC treatment17 (3 mM, n = 63 cells; paired t-test, P < 0.001).

Extended Data Figure 4 Bitter–sour ganglion cells receive taste information from bitter T2R-expressing cells.

Distribution of bitter, sour, and bitter–sour ganglion cells in a sample of control animals (n = 4) and in animals expressing tetanus toxin in PKD2L1-expressing TRCs (PKD2L1-TeNT; n = 3). As expected, no cells responsive to citric acid (50 mM) are detected in PKD2L1-TeNT mice17. However, bitter–sour cells are unaffected (see Fig. 4), suggesting that activation of T2R-expressing TRCs mediates these acidic responses. As predicted, subsequent application of the bitter TRC inactivator AITC17 abolishes bitter responses of the bitter ganglion neurons, as well as the bitter and sour responses in the bitter–sour cells. Note that the solid bars showing less than 1 cell are used to illustrate the lack of responding cells.

Extended Data Figure 5 Representation of taste quality does not cluster within the geniculate ganglion.

a, Two-photon endoscopic image (left) of a geniculate ganglion expressing GCaMP3. Highlighted are the locations of the facial (VII) and greater superficial petrosal (GSP) cranial nerves. The right panel shows approximately 50 neurons colour-coded according to their taste preference in this field. Sour, yellow; sweet, magenta; NaCl, green; bitter, cyan. Scale bar, 200 μm. b, Representative fields of the geniculate ganglion from 6 different mice. The random distribution of neurons representing the various taste qualities is independent of sensor, or method of sensor delivery/expression (AAV-GCaMP6 or Thy1-GCaMP3); colour scheme same as for a.

Extended Data Figure 6 Representation of taste mixtures.

a, Imaging fields of three representative geniculate ganglia illustrating the ensembles of neurons recruited by two different single taste stimuli presented separately (left panels) versus the ensemble of neurons activated by a mixture of the two compounds presented together (right panels). See text for details; as expected there are no mixture-specific responders, and very few cells responded to each tastant in the mix: only 3 out of 113 cells examined with bitter + sweet responded to both tastants, 5 out of 301 cells examined with sour + salty responded to both, and 0 of 39 examined with salty + sweet responded to both tastants. We note that sour stimuli are known to suppress sweet responses30, but such suppression is sweet-cell autonomous and not due to interactions between sweet and sour TRCs (data not shown). b, To quantitatively examine the impact of taste mixes on the responses of individual ganglion neurons, we analysed their response amplitudes in the presence of the single tastant versus the binary mix. Shown are plots of response amplitudes of a representative set of bitter, sweet, salty and sour geniculate neurons stimulated with their selective tastant (x axis) versus their response amplitude when in the presence of an additional tastant (as indicated in the y axis; shown are average ΔF/F over 4 trials). 95% confidence intervals were determined using a ratio t-test: bitter + sweet/bitter, 0.73–0.91; sweet + bitter/sweet, 1.15–1.34; NaCl + sour/NaCl 0.74–1.00; sour + NaCl/sour, 0.95–1.16.

Extended Data Table 1 Shown are the numbers of responding neurons analysed in each of the 14 AAV-GCaMP6s and 15 Thy1–GCaMP3 mice
Extended Data Table 2 The distribution of 971 taste ganglion neurons according to their responses to each of the five basic taste qualities

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Barretto, R., Gillis-Smith, S., Chandrashekar, J. et al. The neural representation of taste quality at the periphery. Nature 517, 373–376 (2015). https://doi.org/10.1038/nature13873

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