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

小鼠的味觉神经编码：将味觉受体与大脑连接起来

• 批准号: 7382489
• 负责人: CHRISTIAN H LEMON
• 金额: $ 2.44万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382489
• 关键词: Acids; Affect; Alleles; Amino Acids; Behavior; Brain; Brain Stem; Categories; Cells; Code; Detection; Diabetes Mellitus; Engineering; Epithelium; Family; G-Protein-Coupled Receptors; Genes; Genetic; Genetic Variation; Genomics; Health; Human; Inbred Strains Mice; Knock-out; Knockout Mice; Knowledge; Label; Ligands; Link; Localized; Logic; Malignant Neoplasms; Mammals; Maps; Measurement; Measures; Mediating; Molecular; Mouse Strains; Mus; Nervous system structure; Neuraxis; Neurons; Obesity; Paper; Pattern; Process; Property; Proteins; Quinine; Receptor Gene; Salts; Son; Specificity; Stimulus; Strychnine; Sucrose; Sweetening Agents; Taste Bud Cell; Taste Perception; Testing; To specify; Ursidae Family; Variant; Wild Type Mouse; base; behavior influence; brucine; cell type; congenic; genetic manipulation; insight; interest; neurobiological mechanism; preference; receptor; relating to nervous system; research study; response; sweet receptor; sweet taste perception

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.

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受体涉及甜味配体的检测。 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表示。然而，对甜味或甜味敏感的 中枢味觉神经元对其他味觉品质刺激的敏感性不同，这就质疑 来自T1r或T2r受体的输入被分离到大脑中特定调谐的细胞。实验在此 这项提议涉及对脑干中单个神经元的味觉反应进行电生理学测量， 对基因Sac或Soa进行靶向操作的小鼠。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，我们将测量神经响应的差异， 甜味刺激在被工程化以携带非功能性Sac等位基因的小鼠（T1r3敲除小鼠）和 野生型小鼠。Soa调节对苦味刺激的敏感性并与T2r苦味共定位 受体基因在目标#2中，将比较两种品系的神经细胞对味觉刺激的神经反应。 基因上只有Soa基因不同的小鼠。这些研究将确定神经元的类别， 对甜或苦刺激的味觉反应受到这些基因的操纵的影响，揭示了细胞 从Sac或Soa的受体产物接收输入的类型。这些鉴定的细胞的特异性 类型将被评估，以确定它们是否可以作为编码通道的味道质量的甜 或者苦或者它们的响应特性是否有利于不同的编码策略。结果将取决于 由Sac和Soa编码的受体介导的味觉信息由神经活动表示。 这些实验将检验Sac或Soa的遗传变异影响中枢味觉的假设， 神经元对不同味觉的刺激物都很敏感。此外，这些实验将 识别大脑中味觉神经元的类别，这些神经元是神经基质的基础， Sac和Soa影响对味觉刺激的行为反应，这将提供对味觉刺激的深入了解。 这些基因控制味觉偏好的神经生物学机制。口味偏好指南 饮食选择导致人类许多健康问题，如癌症、肥胖和糖尿病。