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

描述（由申请人提供）：分子研究最近鉴定了两个味觉受体家族。T1 r受体识别一些甜味或氨基酸刺激物，而T2 r受体则参与检测甜味配体。这些受体的表达模式已经引起了人们对甜味和苦味由神经系统中的专用编码通道代表的想法的兴趣;然而，甜味或甜味反应中枢味觉神经元对其他味觉品质的刺激的敏感性不同，这就质疑了来自T1 r或T2 r受体的输入是否被分离到大脑中的特定调谐细胞。本申请中的实验涉及对基因Sac或Soa进行靶向操作的小鼠脑干中单个神经元的味觉反应的电生理学测量。Sac影响哺乳动物对甜食的偏好，并编码甜味受体T1 r3。在目标1中，我们将测量携带非功能性Sac等位基因的小鼠（T1 r3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T2 r苦味受体基因共定位。在目标2中，将比较两种小鼠对味觉刺激的神经反应，这两种小鼠的遗传差异仅在于基因Soa。这些研究将确定对甜味或苦味刺激的味觉反应受到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。将评价这些鉴定的细胞类型的特异性，以确定它们是否可以作为甜味或苦味的味道品质的编码通道，或者它们的响应特性是否有利于不同的编码策略。结果将影响由Sac和Soa编码的受体介导的味觉信息如何由神经活动表示。这些实验将检验Sac或Soa的遗传变异影响对不同味觉品质的刺激物不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，这些味觉神经元是Sac和Soa影响对味觉刺激的行为反应的神经基质的基础，这将为这些基因控制味觉偏好的神经生物学机制提供深入了解。味觉偏好引导饮食选择，导致人类许多健康问题，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.