The contribution of lateral hypothalamus to cortical palatability coding and behavior

项目摘要 味觉系统的核心工作包括决定是否应该吞咽口中的物质， 拒绝这项工作具有独特的重要性，因为这些决定必须在潜在的有毒物质之后做出。 刺激已经是内部的了。初级味觉皮层（GC）已被证明是至关重要的驱动味觉排斥行为， 但是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性 GC的伴侣是外侧下丘脑（LH），长期以来一直被认为是摄食的中枢参与者 行为，并包含产生两种不同类型的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、通路和 神经元特异性光遗传学，以及复杂的神经和行为分析，以研究GC是否以及如何 和LH协调驱动消耗相关的皮质放电和行为。双部位电生理 将分析清醒的品尝大鼠的反应，以确定LH和GC反应是否以及如何被激活。 耦合生产适口性相关的发射;进一步的工作将确定是否特定的反应类型 或神经元（即，食欲素+神经元，已知驱动消耗）有助于任何观察到的LH-GC偶联。 在品尝过程中干扰LH和GC输入（特别是食欲素+神经元的活动）将测试是否 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 GC-LH合作进行味觉加工和行为输出。在这个项目中，先进的 计算培训将在课堂上获得，并通过开发新的脚本， 具体分析。实验室和布兰迪斯的合作和亲密的环境不仅会滋养 知识基础（计算和超越），但指导，沟通和技术技能 作为一名独立的研究者，行为电生理学和遗传学的结合 这些方法将为味觉系统提供宝贵的见解，最终提高我们对味觉的认识。 味觉系统以及如何进行味觉处理和决策。因为我们直接研究适口性 以及它与行为的关系，这为未来研究与消费有关的疾病扫清了道路， 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.