Lemon Christian H, Margolskee Robert F
Department of Anatomy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
J Neurophysiol. 2009 May;101(5):2459-71. doi: 10.1152/jn.90892.2008. Epub 2009 Mar 11.
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.
T1r3是T1r甜味受体的关键亚基。在此，我们研究了T1r3缺失如何影响小鼠孤束核（NTS）中味觉神经元对甜味刺激的反应。这些结果与甜味受体的多样性以及T1r3如何影响中枢味觉神经元的分布有关。通过电生理学方法记录了麻醉状态下T1r3基因敲除（KO）和野生型（WT）C57BL/6小鼠单个NTS神经元对甘氨酸、蔗糖、氯化钠、盐酸和奎宁的味觉反应。其他刺激物包括L-脯氨酸、D-果糖、D-葡萄糖、D-山梨醇、糖精钠、乙酰磺胺酸钾、味精、硝酸钠、醋酸钠、柠檬酸、氯化钾、苯甲地那铵和罂粟碱。记录了41个WT神经元和41个KO神经元。与WT相比，KO对所有甜味刺激的反应显著降低，尽管不同刺激的衰减程度有所不同，对糖类的反应接近零，但对人工甜味剂和甘氨酸仍有显著的残余活性。通过多变量和相关性分析表明，KO对甜味刺激的跨神经元残余反应与非甜味反应有不同程度的相似性。在某些情况下，这表明对“甜味”刺激的KO残余活性可能由非甜味受体介导，这意味着T1r3受体是NTS甜味处理的主要贡献者。通过比较WT和KO细胞之间出现的神经元类型，评估了T1r3对NTS神经元分布的影响。对甜味刺激有反应的神经元占WT样本的34%，但在KO细胞中未出现。含T1r3受体的输入对朝向甜味剂的NTS神经元的正常发育起着关键的引导作用。
