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

描述（由申请人提供）：分子研究最近确定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受体则涉及检测苦味配体。这些受体的表达模式激发了人们的兴趣：甜味和苦味是由神经系统中专门的编码通道代表的；然而，对甜味或苦味反应的中枢味觉神经元对其他味觉质量刺激的敏感性不同，这就质疑来自T1r或T2r受体的输入是否被隔离到大脑中特定的调谐细胞中。该应用的实验包括通过对基因Sac或Soa进行定向操作，对小鼠脑干中单个神经元的味觉反应进行电生理测量。囊影响哺乳动物对甜食的偏好，并对甜味受体T1r3进行编码。在Aim 1中，我们将测量携带无功能Sac等位基因的小鼠（T1r3基因敲除小鼠）和野生型小鼠对甜味刺激的神经反应差异。Soa调节对苦味刺激的敏感性，并与T2r苦味受体基因共定位。在目标2中，将比较两种基因仅在Soa基因上不同的小鼠对苦味刺激的神经反应。这些研究将确定对甜味或苦味刺激的味觉反应受这些基因操纵影响的神经元类别，揭示从Sac或Soa受体产物接收输入的细胞类型。这些已鉴定的细胞类型的特异性将被评估，以确定它们是否可以作为甜或苦的味道质量的编码通道，或者它们的响应特性是否有利于不同的编码策略。结果将与Sac和Soa编码的受体介导的味觉信息如何通过神经活动表示有关。这些实验将验证Sac或Soa的遗传变异会影响对不同口味刺激敏感的中枢味觉神经元的假设。此外，这些实验将确定大脑中味觉神经元的类别，这些类别是神经基质的基础，Sac和Soa通过这些神经基质影响对味觉刺激的行为反应，这将为这些基因控制味觉偏好的神经生物学机制提供见解。口味偏好引导着饮食选择，导致人类出现许多健康问题，如癌症、肥胖和糖尿病。

DESCRIPTION (provided by applicant): 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 in this application 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.