The contribution of lateral hypothalamus to cortical palatability coding and behavior

项目摘要 味觉系统的中心工作包括决定口腔中的物质是应该吞下还是应该 被拒绝了。这项工作具有独特的重要性，因为这些决定必然是在一个潜在的有毒事件之后做出的 刺激措施已经是内部的。初级味觉皮质(GC)已被证明对驱动味觉拒绝行为至关重要 但GC不太可能单独行动来完成这项任务。作为一种可能的功能 GC的伙伴是下丘脑外侧核，长期以来一直被认为是参与摄食的中枢 它包含产生两种不同类型的与适口性相关的味觉反应的神经元。这 提案描述了将使用多电极电生理学、肌电图仪、通路和 神经元特定的光遗传学，以及复杂的神经和行为分析，以调查GC是否以及如何 和黄体生成素协调来驱动与消费相关的皮质激发和行为。双部位电生理 将分析清醒的品尝大鼠的反应，以确定促黄体生成素和卵泡刺激素的反应是否以及如何 用于产生与适口性相关的激发；进一步的工作将确定特定的反应类型 或神经元(即，食欲素神经元，已知的驱动消费)有助于任何观察到的黄体生成素-GC偶联。 在品尝过程中干扰促黄体生成素GC输入(特别是食欲素神经元的活动)将测试 以及下丘脑输入如何影响GC味觉反应动力学。这些实验将是第一次探索 进入GC-LH协作进行味觉处理和行为输出。在这个项目的过程中，高级 计算培训将在课堂上获得，并通过开发新的脚本来实现 具体分析。实验室内和布兰代斯的协作和亲密环境不仅将滋养 知识基础(计算和其他)，但指导、沟通和技术技能 需要发展成为一名独立的研究人员。行为学、电生理学和遗传学的结合 方法将为味觉系统提供宝贵的洞察力，最终提高我们对 味觉系统以及味觉处理和决定是如何做出的。因为我们正在直接调查适口性 及其与行为的关系这为未来研究与消费和行为相关的障碍扫清了道路 享乐主义。因此，这项工作与在这个肥胖和暴饮暴食的时代改善人类健康有关。

Project Summary The central job of the taste system involves deciding whether a substance in the mouth should be swallowed or rejected. This job is of unique importance, in that these decisions are necessarily made after a potentially toxic stimulus is already internal. Primary gustatory cortex (GC) has proven vital for driving taste rejection behavior in situ, but it is unlikely GC is acting alone to accomplish this task. Of particular interest as a possible functional partner to GC is the lateral hypothalamus (LH), which has long been known to be centrally involved in feeding behavior, and which contains neurons producing two distinct types of palatability-related taste responses. This proposal describes work that will use multi-electrode electrophysiology, electromyography, pathway- and neuron-specific optogenetics, and complex neural and behavioral analyses to investigate whether and how GC and LH coordinate to drive consumption-related cortical firing and behavior. Dual-site electrophysiological responses from awake, tasting rats will be analyzed to determine whether and how LH and GC responses are coupled for production of palatability-related firing; further work will determine whether particular response types or neurons (i.e., orexin+ neurons, known to drive consumption) contribute to any observed LH-GC coupling. Perturbing LHGC input (and specifically the activity of orexin+ neurons) during tasting sessions will test whether and how hypothalamic input impacts GC taste response dynamics. These experiments will be the first exploration into GC-LH cooperation for taste processing and behavioral output. Over the course of this project, advanced computational training will be acquired both in the classroom and through the development of novel scripts for specific analyses. The collaborative and intimate environment within the lab and at Brandeis will nourish not only the knowledgebase (computational and beyond), but the mentorship, communication, and technical skills required to develop as an independent researcher. The combination of behavior, electrophysiology, and genetic approaches will provide invaluable insight to the taste system, ultimately improving our knowledge of the gustatory system and how taste processing and decisions are made. As we are directly investigating palatability and its relationship to behavior this clears the path for future research on disorders related to consumption and hedonics. As such, the work is related to improving human health in this era of obesity and binge-eating.