Encoding of behaviorally relevant olfactory stimuli

描述(申请人提供)：哺乳动物已经进化出双重嗅觉系统来检测大量的气味和信息素，并将化学信息转化为不同的感知和不同的行为。最近的研究表明，主嗅觉系统和辅助嗅觉系统都参与了一般气味和信息素的检测，但每个系统在调节不同嗅觉行为中的不同作用尚不清楚。此外，尽管在这两个系统中对气味检测、感觉转导和信息编码的理解都取得了长足的进步，但无论是引起不同嗅觉行为的气味刺激，还是介导气味特异性神经和内分泌反应的大脑神经通路都没有明确的定义。这项提议将开发分子技术来识别由行为相关的嗅觉刺激激活的气味或信息素受体，以检验这样一种假设，即生物上有意义的嗅觉刺激是由不同的气味或信息素受体亚类检测到的。对行为激活受体的识别将使未来的研究能够：1)筛选不同的气味部分和单个气味成分，以揭示具有生物学意义的嗅觉刺激的身份；2)剖析两个嗅觉系统在调节特定嗅觉行为方面的相对作用；3)表征来自这些受体的信号如何在大脑中传递，以调节不同的行为。许多嗅觉行为都是强健的和刻板的，而调节这些行为反应的神经回路在很大程度上是由基因决定的。了解调节这些先天行为的神经底物将有助于我们理解正常的人类行为以及神经发育障碍，如自闭症、精神分裂症和药物成瘾。

DESCRIPTION (provided by applicant): Mammals have evolved dual olfactory systems to detect a vast number of odorants as well as pheromones, and to translate chemical information into diverse perceptions and distinct behaviors. Recent studies have shown that both the main and the accessory olfactory systems are involved in detecting both general odors and pheromones, but the distinct roles of each system in mediating different olfactory behaviors remain to be characterized. In addition, despite considerable progress in understanding odor detection, sensory transduction and information coding in both systems, neither the odor stimuli that elicit distinct olfactory behaviors nor the brain neural pathways that mediate odor-specific neural and endocrine responses have been clearly defined. This proposal will develop molecular techniques to identify odorant or pheromone receptors activated by behaviorally relevant olfactory stimuli to test the hypothesis that biologically significant olfactory stimuli are detected by distinct subsets of odorant or pheromone receptors. Identification of behaviorally-activated receptors will allow future studies to: 1) screen different odor fractions and individual odor components to reveal the identity of biologically significant olfactory stimuli, 2) dissect the relative roles of the two olfactory systems in regulating specific olfactory behaviors, and 3) characterize how signals from these receptors are routed in the brain to regulate distinct behaviors. Many olfactory behaviors are robust and stereotyped, and the neural circuits mediating these behavioral responses are largely genetically determined. Knowledge of the neuronal substrates mediating these innate behaviors will aid our understanding of normal human behavior as well as neurodevelopmental disorders such as autism, schizophrenia and drug addiction.