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.

项目总结 泪液分泌(流泪)是润滑我们的眼睛和帮助减少眼睛的一个基本机制 刺激物和微生物感染。泪液不足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、先天性白化病和病毒感染。以前的研究 提示上唾液核(SSN)控制泪水分泌。然而，直接的分子和 目前尚缺乏基因证据。我们最近在小鼠SSN中发现了一个高度受限的神经元群体。烧蚀 显著地减少了小鼠的泪水，这表明这个神经元群体 控制流泪。为了验证这一假设，我们将首先确定传出目标和生理 这些SSN神经元的特性(目标1)。这些实验的结果将提供有价值的信息 关于泪液信号的编码和传输。第二，我们将调查这些SSN的作用 神经元通过特定的消融或激活这个神经元群体来控制流泪(目标2)。结果 这些实验将为SSN控制催泪作用提供功能依据。最后，我们将测试这些 SSN神经元接受来自眼表的感觉输入，并介导反射性撕裂(目标3)。结果来自 这些实验将有助于确定以前未被识别的眼睛感觉输入和SSN之间的联系， 为反射性流泪背后的神经机制提供了新的见解。总而言之，我们的建议 研究将有助于揭示泪水的神经回路，并为未来的研究提供基础知识 与眼部或全身疾病有关的泪水缺乏。