Neural Circuits Controlling Lacrimation

控制流泪的神经回路

• 批准号: 10718512
• 负责人: Qin Liu
• 金额: $ 46.48万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718512
• 关键词: Ablation; Address; Afferent Pathways; Allergens; Autonomic Dysfunction; Axon; Biological Assay; Bombesin Receptor; Brain Stem; Calcium; Cell Nucleus; Clinical; Disease; Efferent Pathways; Electrophysiology (science); Etiology; Eye; Eye diseases; Fiber; Functional disorder; Future; Ganglia; Genetic; Image; Infection; Irritants; Knowledge; Lacrimation; Lead; Lubrication; Lupus; Mediating; Molecular; Mus; Nerve; Neuronal Dysfunction; Neurons; Pathway interactions; Physiological; Pilot Projects; Population; Population Control; Preganglionic Autonomic Fibers; Property; Reflex action; Research; Role; Sensory; Signal Transduction; Sjogren' s Syndrome; Synapses; Systemic disease; Testing; Virus Diseases; experimental study; eye dryness; insight; irritation; lacrimal; loss of function; microbial; neural circuit; neuromechanism; neurotransmitter release; new therapeutic target; novel; ocular surface; optogenetics; pathogen; pharmacologic; response; saliva secretion; sensory input; transmission process

PROJECT SUMMARY Tear secretion (lacrimation) is an essential mechanism that lubricates our eyes and helps reduce eye irritants and microbial infections. Lacrimal deficiency is associated with many systemic or ocular diseases including primary Sjögren's syndrome, lupus, dry eyes, congenital alacrima, and viral infections. Previous studies have suggested that the superior salivatory nucleus (SSN) controls lacrimation. However, direct molecular and genetic evidence is lacking. We recently identified a highly restricted neuronal population in mouse SSN. Ablation of this neuronal population remarkably reduces lacrimation in mice, suggesting that this neuronal population controls lacrimation. To test this hypothesis, we will first determine the efferent targets and physiological properties of these SSN neurons (Aim 1). Results from these experiments will provide valuable information regarding the encoding and transmission of lacrimal signals. Second, we will investigate the role of these SSN neurons in controlling lacrimation by specific ablation or activation of this neuronal population (Aim 2). Results from these experiments will provide functional evidence for SSN control of lacrimation. Finally, we will test these SSN neurons receive sensory inputs from ocular surface and mediate reflex lacrimation (Aim 3). Results from these experiments will help define previously unrecognized connections between ocular sensory inputs and SSN, offering novel insights into the neural mechanism underlying the reflex lacrimation. In summary, our proposed research will help reveal the neural circuit for lacrimation and provide foundational knowledge for future studies of lacrimation deficiency associated with ocular or systemic diseases.

项目概要 泪液分泌（流泪）是润滑眼睛并有助于减少眼睛疲劳的重要机制。 刺激物和微生物感染与许多全身或眼部疾病有关。 包括原发性干燥综合征、狼疮、干眼症、先天性流泪症和病毒感染。 已经表明上唾液核（SSN）控制流泪，但是，直接分子和控制。 我们最近在小鼠 SSN 中发现了高度受限的神经元群。 该神经群显着减少了小鼠的流泪，表明该神经群 为了检验这个假设，我们首先确定传出目标和生理学。 这些 SSN 神经元的特性（目标 1）将提供有价值的信息。 其次，我们将研究这些 SSN 的作用。 通过特定消融或激活该神经元群来控制流泪的神经元（目标 2）。 这些实验将为 SSN 控制流泪提供功能证据。最后，我们将测试这些。 SSN 神经元接收来自眼表面的感觉输入并介导反射性流泪（目标 3）。 这些实验将有助于定义以前未认识到的眼部感觉输入和 SSN 之间的联系， 总而言之，我们提出了对反射性流泪背后的神经机制的新见解。 研究将有助于揭示流泪的神经回路，并为未来的研究提供基础知识 与眼部或全身疾病相关的流泪不足。