Deconstructing brainstem circuits for visceral senses

解构内脏感觉的脑干回路

• 批准号: 10591627
• 负责人: Chen Ran
• 金额: $ 12.58万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10591627
• 关键词: Anatomy; Animals; Anorexia; Atlases; Behavior; Behavior Control; Behavioral; Brain; Brain Stem; Brain region; Calcium; Cardiovascular Physiology; Cardiovascular system; Categories; Cell Nucleus; Code; Complex; Cues; Data; Desire for food; Diabetes Mellitus; Digestive Physiology; Disease; Eating; Eating Disorders; Efferent Pathways; Emetics; Energy Metabolism; Feedback; Feeding behaviors; Food; Gastrointestinal tract structure; Genetic; Goals; Health; Homeostasis; Hormones; Hunger; Hypothalamic structure; Image; Individual; Inflammatory; Ingestion; Intestines; Irritants; Label; Logic; Manuscripts; Maps; Mediating; Metabolic; Metabolic Control; Metabolism; Monitor; Motor Neurons; Mus; Nature; Nausea; Nervous System; Neuroanatomy; Neurons; Nucleus solitarius; Nutrient; Obesity; Organ; Pathway interactions; Pattern; Peer Review; Perception; Physiological; Physiology; Play; Population; Postdoctoral Fellow; Process; Property; Research; Respiratory System; Respiratory physiology; Role; Satiation; Scientist; Sensory; Signal Transduction; Sorting; Specificity; Stimulus; Stomach; System; Taste aversion; Therapeutic; Time; Toxin; Vagus nerve structure; Viral; Visceral; Visceral pain; Water consumption; Work; cell type; conditioned place preference; detection platform; experimental study; feeding; flyer; gastrointestinal; gastrointestinal system; genetic approach; imaging platform; in vivo; in vivo calcium imaging; insight; mechanical signal; nerve supply; neural; neural circuit; neuroregulation; neurotransmission; novel; optogenetics; paraventricular nucleus; respiratory; response; segregation; sensory system; tool; transmission process; two-photon; virus genetics

PROJECT SUMMARY/ABSTRACT The ability to tightly control metabolic homeostasis is critical for animal survival. The internal sensory nervous system monitors the status of organs, providing feedback signals that enable the brain to maintain homeostasis by executing behavioral and physiological responses. For example, the system detects and encodes gastrointestinal cues signaling the quality and quantity of food ingested during a meal to control feeding behavior, digestive physiology, and whole-body metabolism. Dysregulation of internal sensory systems that monitor the digestive system can lead to various diseases, including obesity, diabetes, and anorexia. The internal sensory gateway in the brainstem, the nucleus of the solitary tract (NTS), receives inputs from the gastrointestinal, respiratory, and cardiovascular systems through the vagus nerve and other neural/humoral pathways. In turn, the NTS projects to diverse higher-order brain regions to generate our perceptions of satiety, hunger, nausea, and visceral pain. Despite the importance of internal sensory systems in health and disease, how neural circuits process visceral signals to regulate behavior and physiology is vastly understudied. Disentangling the highly interconnected brainstem neurons requires a comprehensive analysis of the anatomy, sensory coding, and function of the NTS network to understand the circuit components that mediate individual visceral senses. In Dr. Stephen Liberles’ lab, my initial postdoctoral work deciphered the sensory representations of bodily cues in the NTS. In this proposal, the goal is to determine how internal sensory information, after being processed in the NTS, is sorted into downstream brain regions to control specific aspects of behavior and physiology. First, the neuroanatomical logic by which NTS projections are organized will be investigated (Aim 1). Second, visceral cues transmitted by each projection will be determined using in vivo calcium imaging of NTS projection neurons (Aim 2). Last, the functional roles of NTS projections in controlling behavior and autonomic physiology will be established, with the focus on pathways that mediate physiological satiation (Aim 3). Research in this proposal will be conducted under the guidance of Dr. Stephen Liberles, who pioneered the study of viscerosensory neurons in the vagus nerve using genetic approaches, Dr. Clifford Saper, a leading scientist in the neuroanatomy of the viscerosensory system, and Drs. Bradford Lowell and Eleftheria Maratos-Flier, experts in neural control of appetite and energy metabolism. This proposal will establish a functional atlas of NTS projection neurons in visceral senses, providing insights into our understanding of the neuro-circuitry underlying metabolic homeostasis and strategies to develop targeted treatments for metabolic and viscerosensory disorders.

项目摘要/摘要 严格控制代谢稳态的能力对于动物生存至关重要。内部感觉神经 系统监视器官的状态，提供反馈信号，使大脑保持体内平衡 通过执行行为和身体反应。例如，系统检测和编码 胃肠线暗示餐食中摄入的食物的质量和数量以控制喂养行为， 消化生理和全身代谢。内部感觉系统的失调，监视 消化系统会导致各种疾病，包括肥胖，糖尿病和厌食症。内部感觉系统会导致各种疾病，包括肥胖，糖尿病和厌食症。 脑干中的网关，固体道（NTS）的核从胃肠道接收的输入， 通过迷走神经和其他神经/体液途径的呼吸道和心血管系统。反过来， NTS向潜水高级大脑区域投射，以产生我们对饱腹感，饥饿，恶心， 和内脏疼痛。尽管内部感觉系统在健康和疾病中很重要，但神经回路如何 众所周知，要调节行为和生理的过程内脏信号。高度解开 互连的脑干神经元需要对解剖学，感觉编码和 NTS网络的功能以了解媒体个体内脏感觉的电路组件。在Dr. 斯蒂芬·利伯尔斯（Stephen Liberles）的实验室，我最初的博士后作品决定了人身线索的感官表征 NTS。在此提案中，目标是确定内部感官信息如何在 NTS分类为下游大脑区域，以控制行为和生理学的特定方面。首先， 将研究NTS项目的神经解剖学逻辑（AIM 1）。第二，内脏 每个投影传递的提示将使用NTS投影神经元的体内钙成像确定 （目标2）。最后，NTS项目在控制行为和自主生理学中的功能作用将是 建立，重点是介导物理疾病的途径（AIM 3）。该提议的研究 将在Stephen Liberles博士的指导下进行，后者开创了内脏的研究 神经术的主要科学家Clifford Saper博士使用遗传方法中的神经元神经元 内脏感系统和Drs的Bradford Lowell和Eleftheria Maratos-Flier，神经控制专家 食欲和能量代谢。该建议将在 内脏的感觉，为我们对我们对神经通路的理解提供见解 稳态和开发针对代谢和内脏感染疾病的有针对性治疗的策略。