Investigation of a candidate chemotherapy-induced nausea sensory circuit

描述（由申请人提供）：化疗引起的恶心对生活质量产生负面影响，可以改变对化疗治疗计划的依从性，并且反复被列为开始癌症治疗的患者的最大恐惧。这个项目的目标是更好地了解感觉系统和分子机制参与检测刺激导致产生恶心。我们希望能定义一个分子上未探索的感觉回路及其在调节生物体行为和生理中的作用。最有效的抗恶心药物类别靶向在迷走神经的感觉成分中优先表达的5-羟色胺受体。然而，这些纤维的神经支配的解剖学分布仍然未知，操纵这个回路对行为的影响也是如此。我将使用遗传学工具，包括小鼠转基因系和腺病毒载体基因传递，专门映射解剖和功能操纵候选恶心电路。该系统的检查将打开基础研究到一个不好的特点和临床相关的感觉系统，也提供了潜在的替代目标的高度相关的许多患者的治疗干预。

DESCRIPTION (provided by applicant): Chemotherapy-induced nausea negatively impacts quality of life, can alter adherence to chemotherapeutic treatment plans, and is repeatedly ranked as the greatest fear by patients beginning cancer treatment. The goal of this project is to better understand the sensory systems and molecular mechanisms involved in detection of stimuli leading to generation of nausea. We hope to define a molecularly unexplored sensory circuit and its role in modulating organism behavior and physiology. The most efficacious anti-nausea medication class target serotonin receptors preferentially expressed in the sensory component of the vagus nerve. However, the anatomical distribution of innervation by these fibers remains unknown, as does the effect of manipulating this circuitry on behavior. I will use genetic tools including mouse transgenic lines and adenoviral vector gene delivery to specifically map the anatomy and functionally manipulate candidate nausea circuits. Examination of this system will open basic research into a poorly characterized and clinically relevant sensory system, and also provide potential alternative targets for therapeutic intervention of high relevance to many patients.