Neural mechanisms of taste and metabolic state integration in the brainstem

脑干味觉和代谢状态整合的神经机制

• 批准号: 10524319
• 负责人: Nilay Yapici
• 金额: $ 71.87万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524319
• 关键词: Acute; Affect; Animals; Area; Behavior; Biology; Brain; Brain Stem; Brain imaging; Brain region; Cell Nucleus; Cerebellum; Code; Collaborations; Consumption; Cranial Nerves; Data Set; Detection; Eating; Evaluation; Feeding behaviors; Food; Homeostasis; Hunger; Hypothalamic structure; Image; Ingestion; Insula of Reil; Knowledge; Lead; Location; Mammals; Mediating; Metabolic; Monitor; Mus; Nerve Fibers; Neurons; Nucleus solitarius; Operative Surgical Procedures; Optics; Organ; Organism; Palate; Pathway interactions; Perception; Peripheral; Pharyngeal structure; Photons; Population; Positioning Attribute; Regulation; Research; Research Personnel; Resolution; Resource Sharing; Sensory; Signal Transduction; Somatostatin; Source; Taste Perception; TimeLine; Tongue; Ventral Tegmental Area; awake; base; behavior measurement; calretinin; design; experimental study; food consumption; food resource; implantation; in vivo calcium imaging; indexing; lens; microendoscope; microendoscopy; neuromechanism; neuronal circuitry; novel; optogenetics; relating to nervous system; response; sugar

ABSTRACT The taste of food is a critical factor that determines whether an organism will accept or reject a food source. In addition, the sensory perception of food taste changes significantly depending on the metabolic state of animals. Despite the significant progress in understanding the homeostatic biology of food intake in the mammalian brain, how metabolic states (e.g., how hungry an animal is) alter the perception of food taste at the level of specific neuronal circuits remains poorly understood. Here, we assembled a team of investigators that will use quantitative measurements of behavior, cutting edge 3P microendoscopy, and optogenetic manipulation of neural activity to study how taste representations in the brainstem are modulated with metabolic state, and how the state dependent activity of brainstem taste circuits contributes to the regulation of ingestive behaviors in mice. Specifically, this new team of investigators will probe the functions and the state dependent activity of two distinct populations of neurons, sugar sensitive calbindin 2- neurons (Calb2) and bitter sensitive somatostatin- neurons (Sst), in the rostral nucleus solitary tract (rNTS), the first central relay station of the taste pathway. In Aim 1 the investigators will develop and optimize a state of the art 3-photon (3P) microendoscope that will allow optical access to Calb2 and Sst neurons in the rNTS at cellular resolution. In Aim 2, the 3P microendoscope will be used to examine the taste responses of Calb2 and Sst neurons in hungry and sated mice to investigate whether sugar or bitter responses are modulated in response to changes in metabolic state. In Aim 3, the investigators will investigate whether acute changes in the hunger state of mice affect the taste representations in the rNTS by artificially modulating the activity of hunger promoting AgRP neurons in the hypothalamus. More specifically, they will record the activity of Calb2 or Sst neurons using the 3P microendoscope, while optogenetically activating or inhibiting AgRP neurons of sated or hungry mice that are offered a sugar solution or sugar plus bitter mixture. The proposed study will provide critical information for understanding a core mechanism of taste and metabolic state integration in the brainstem. It will also allow the team to investigate whether taste coding is modulated in the brainstem based on metabolic state before the information is sent to higher-order gustatory nuclei and to the insula cortex in a feed-forward fashion. Together, the proposed experiments will generate novel knowledge and provide necessary technical and conceptual advances to lay the groundwork for a subsequent Targeted BRAIN Circuits R01 with the same team of investigators aiming to further investigate how brainstem taste circuits communicate with other central gustatory nuclei in a metabolic state dependent manner to control ingestive behaviors in mice.

抽象的 食物的味道是确定生物体是否接受或拒绝食物来源的关键因素。在 此外，食物口味的感觉感知明显变化，具体取决于动物的代谢状态。 尽管了解哺乳动物大脑中食物摄入的稳态生物学方面取得了重大进展，但 代谢状态（例如，动物的饥饿程度）如何改变特定水平的食物味道的感知 神经元电路的理解仍然很差。在这里，我们组建了一个调查人员团队，将使用 对行为的定量测量，尖端3p微观镜检查和光学遗传操作的定量测量 神经活动以研究如何通过代谢状态调节脑干中的味觉表征以及如何 脑干味道电路的状态依赖活动有助于调节摄取行为 老鼠。具体而言，这个新的调查人员团队将调查两个功能和国家依赖活动 神经元的不同种群，糖敏感的钙蛋白酶2-神经元（CalB2）和苦敏感的生长抑素 - 神经元（SST），鼻核孤立区（RNTS），味觉途径的第一个中央继电器站。在 AIM 1研究人员将开发并优化一种最先进的3-Photon（3p）微镜镜，该状态将允许 在细胞分辨率下，RNT中对CalB2和SST神经元的光学访问。在AIM 2中，3p微型镜将 用于检查饥饿和饥饿小鼠中calb2和SST神经元的味道反应，以调查 糖或苦味反应是针对代谢状态变化而调节的。在AIM 3中 调查人员将调查小鼠饥饿状态的急性变化是否影响味觉表示 在RNT中，通过人为地调节下丘脑中促进AGRP神经元的饥饿活性。更多的 具体而言，他们将使用3P微型镜检查记录Calb2或SST神经元的活性，而 提供糖溶液的光遗传学激活或抑制为糖或饥饿的小鼠的AGRP神经元 或糖加苦的混合物。拟议的研究将为理解核心提供关键信息 脑干中的味道和代谢状态整合的机理。这也将允许团队调查 在发送信息之前，是否基于代谢状态在脑干中调制口味编码 高阶味道核和以馈送方式到达绝缘皮层。一起，提议 实验将产生新颖的知识，并提供必要的技术和概念进步来奠定 随后有针对性的大脑电路R01的基础工作，同一调查人员旨在进一步 研究脑干味道电路如何与其他中央味道核在代谢状态进行通信 控制小鼠的摄入行为的依赖方式。