Neural Circuits Controlling Lacrimation

项目摘要 泪液分泌（流泪）是润滑我们的眼睛并帮助减少眼睛的重要机制。 刺激物和微生物感染。泪液缺乏与许多系统性或眼部疾病有关 包括原发性干燥综合征、狼疮、干眼症、先天性无泪症和病毒感染。以前的研究 已经提出上级唾液核（SSN）控制流泪。然而，直接分子和 缺乏遗传学证据。我们最近发现了一个高度限制的神经元群体在小鼠SSN。消融 这种神经元群体显着减少小鼠的流泪，表明这种神经元群体 控制流泪。为了验证这一假设，我们将首先确定传出靶点和生理靶点。 这些SSN神经元的特性（目的1）。这些实验的结果将提供有价值的信息 关于泪腺信号的编码和传输。其次，我们将研究这些SSN的作用 通过特异性消融或激活该神经元群体来控制流泪的神经元（目的2）。结果 为SSN控制流泪提供了功能性证据。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流泪（Aim 3）。结果 这些实验将有助于确定以前未被认识到的视觉感觉输入和SSN之间的联系， 提供了新的见解神经机制的反射流泪。综上所述，我们的建议 这项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 与眼部或全身性疾病相关的流泪缺陷。

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.