Contribution of the T1r3 Taste Receptor to the Response Properties of Central Gustatory Neurons

T1r3 is a critical subunit of T1r sweet taste receptors. Here we studied how the absence of T1r3 impacts responses to sweet stimuli by taste neurons in the nucleus tractus solitarius (NTS) of the mouse. The consequences bear on the multiplicity of sweet taste receptors and how T1r3 influences the distribution of central gustatory neurons. Taste responses to glycine, sucrose, NaCl, HCl, and quinine were electrophysiologically recorded from single NTS neurons in anesthetized T1r3 knockout (KO) and wild-type (WT) C57BL/6 mice. Other stimuli included l-proline, d-fructose, d-glucose, d-sorbitol, Na-saccharin, acesulfame-K, monosodium glutamate, NaNO(3), Na-acetate, citric acid, KCl, denatonium, and papaverine. Forty-one WT and 41 KO neurons were recorded. Relative to WT, KO responses to all sweet stimuli were significantly lower, although the degree of attenuation differed among stimuli, with near zero responses to sugars but salient residual activity to artificial sweeteners and glycine. Residual KO across-neuron responses to sweet stimuli were variably similar to nonsweet responses, as indexed by multivariate and correlation analyses. In some cases, this suggested that residual KO activity to "sweet" stimuli could be mediated by nonsweet taste receptors, implicating T1r3 receptors as primary contributors to NTS sweet processing. The influence of T1r3 on the distribution of NTS neurons was evaluated by comparing neuron types that emerged between WT and KO cells. Neurons tuned toward sweet stimuli composed 34% of the WT sample but did not appear among KO cells. Input from T1r3-containing receptors critically guides the normal development of NTS neurons oriented toward sweet tastants.