Gustatory neural coding in mice: connecting taste receptors to the brain

分子研究最近发现了两个味觉受体家族。T1R受体识别一些 甜味或氨基酸刺激，而T2R受体与苦味配体的检测有关。 这些受体的表达模式激发了人们对甜味和苦味的兴趣 由神经系统中的专用编码通道代表。然而，对甜味或苦味的反应 中枢味觉神经元对其他味觉刺激的敏感度不同，这就质疑了 来自T1R或T2R受体的输入被分离到大脑中特定的调谐细胞。在此基础上的实验 建议对脑干单个神经元的味觉反应进行电生理学测量。 靶向操纵SAC或SoA基因的小鼠。SAC影响哺乳动物对甜食的偏好 并编码甜味受体T1R3。在目标1中，我们将测量神经反应的差异 携带非功能性SAC等位基因的小鼠(T1R3基因敲除小鼠)和 野生型老鼠。SOA调节对苦味刺激的敏感性，并与T2R苦味共同定位 受体基因。在目标2中，将比较两种品系的神经对苦味刺激的反应。 只有SoA基因不同的小鼠。这些研究将确定神经元的类别 对甜味或苦味刺激的味觉反应受到这些基因操作的影响，揭示了细胞 从SAC或SoA的受体产品接收输入的类型。这些已鉴定细胞的特异性 将对类型进行评估，以确定它们是否可以作为甜味品质的编码通道 或苦涩的，或者如果它们的响应特性有助于不同的编码策略。结果将取决于 味觉信息由SAC和SOA编码的受体介导，由神经活动来表达。 这些实验将检验SAC或SOA基因变异影响中枢味觉的假设 神经元对不同口味的刺激具有不同的敏感性。此外，这些实验将 确定大脑中味觉神经元的类别，这些神经元是神经底物的基础，通过 SAC和SOA影响对味觉刺激的行为反应，这将为深入了解 这些基因控制味觉偏好的神经生物学机制。品味偏好指南 饮食选择会导致人类许多健康问题，如癌症、肥胖症和糖尿病。

Molecular studies have recently identified two families of taste receptors. The T1r receptors recognize some sweet or amino acid stimuli whereas T2r receptors are implicated for the detection of bitter-tasting ligands. The expression patterns of these receptors have invigorated interest in the idea that sweet and bitter taste are represent by dedicated coding channels in the nervous system. However, sweet- or bitter-responsive central gustatory neurons vary in their sensitivities to stimuli of other taste qualities, which questions whether input from T1r or T2r receptors is segregated to specifically-tuned cells in the brain. Experiments under this proposal involve electrophysiological measurement of taste responses in single neurons in the brain stem in mice with targeted manipulation of the gene Sac or Soa. Sac influences preference for sweets in mammals and encodes the sweet taste receptor T1r3. In Aim #1, we will measure differences in neural responding to sweet-tasting stimuli between mice engineered to carry a non-functional Sac allele (T1r3 knockout mice) and wild-type mice. Soa regulates sensitivity to bitter-tasting stimuli and co-localizes with the T2r bitter taste receptor genes. In Aim #2, neural responses to bitter-tasting stimuli will be compared between two strains of mice that genetically differ at only the gene Soa. These studies will identify categories of neurons in which taste responses to sweet or bitter stimuli are influenced by the manipulation of these genes, revealing cell types that receive input from the receptor products of Sac or Soa. The specificity of these identified cell types will be evaluated to determine if they could function as coding channels for the taste qualities of sweet or bitter or if their response properties are conducive to a different coding strategy. Results will bear on how taste information mediated by the receptors encoded by Sac and Soa is represented by neural activity. These experiments will test the hypothesis that genetic variation at Sac or Soa influences central gustatory neurons that are variably sensitive to stimuli of different taste qualities. Moreover, these experiments will identify categories of gustatory neurons in the brain that are fundamental to the neural substrates by which Sac and Soa influence behavioral responding towards taste stimuli, which will provide insight into the neurobiological mechanisms by which these genes control taste preference. Taste preferences guide dietary choices leading to many health problems in humans, such as cancer, obesity and diabetes.