The contribution of lateral hypothalamus to cortical palatability coding and behavior

下丘脑外侧对皮质适口性编码和行为的贡献

• 批准号: 10622323
• 负责人: Kathleen C Maigler
• 金额: $ 3.37万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-16 至 2025-05-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622323
• 关键词: Animals; Appearance; Automobile Driving; Axon; Back; Behavior; Behavioral; Binge Eating; Cells; Code; Communication; Complex; Computational Technique; Consumption; Coupled; Coupling; Cues; Data; Decision Making; Deglutition; Dependence; Development; Disease; Electrodes; Electromyography; Electrophysiology (science); Environment; Feeding behaviors; Feeds; Food; Genetic Techniques; Health; Human; Hypothalamic structure; In Situ; Interruption; Intervention; Jaw; Knowledge; Lateral; Measures; Mentorship; Muscle; Neurons; Obesity; Occupations; Oral cavity; Output; Pathway interactions; Population Dynamics; Production; Prosencephalon; Rattus; Research Personnel; Sensory; Site; Source; Specificity; Stimulus; Taste Perception; Technical Expertise; Techniques; Testing; Time; Toxin; Training; Work; awake; cell cortex; cell type; experimental study; feeding; genetic approach; hedonic; hypocretin; improved; in vivo; insight; interest; knowledgebase; neural; novel; optogenetics; response; sensory system; taste system

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.

项目摘要 口味系统的核心工作涉及确定是否应吞咽口腔中的物质或 被拒绝。这项工作至关重要，因为这些决定是在潜在有毒之后做出的 刺激已经是内部的。事实证明，原发性糖皮质（GC）对于推动口味排斥行为至关重要 原位，但是GC不太可能单独采取行动来完成这项任务。特别感兴趣的功能 GC的合作伙伴是下丘脑（LH），长期以来一直在中心参与进食 行为，其中包含神经元产生两种不同类型的与可口相关的味觉反应。这 提案描述了将使用多电极电生理学，肌电图，途径和途径的工作 神经特异性的光遗传学以及复杂的神经元和行为分析，以研究GC是否以及如何 LH协调以驱动与消费相关的皮层射击和行为。双位点电生理 清醒的反应，品尝大鼠将进行分析，以确定LH和GC的反应是如何以及如何 结合生产与可口相关的射击；进一步的工作将确定特定响应类型是否 或神经元（即，已知可以驱动消耗的Orexin+神经元）有助于任何观察到的LH-GC耦合。 在品尝会议期间，扰动LHGC输入（特别是Orexin+神经元的活性）将测试是否是否测试 以及下丘脑的输入如何影响GC味觉反应动态。这些实验将是第一次探索 进入GC-LH协调，以进行味觉处理和行为输出。在这个项目的过程中，高级 计算培训将在课堂和开发新颖脚本的开发中获得 具体分析。实验室和布兰代斯内部的协作和亲密环境不仅会滋养 知识库（计算及以后），但精通，沟通和技术技能 必须发展为独立研究人员。行为，电生理学和遗传学的结合 方法将为品味系统提供宝贵的见解，最终提高我们对 味道系统以及如何制定口味处理和决策。因为我们直接调查了可口 它与行为的关系清除了与消费有关的疾病的未来研究的途径 享乐者。因此，这项工作与在这个肥胖和暴饮暴食时代的时代改善人类健康有关。