Trigeminal-autonomic relations in ocular homeostasis

眼稳态中的三叉神经自主关系

• 批准号: 8240030
• 负责人: DAVID A BEREITER
• 金额: $ 37.17万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240030
• 关键词: Acids; Affect; Autonomic nervous system; Biological Models; Blood Vessels; Blood flow; Brain; Brain Stem; Caliber; Cell Nucleus; Cervical; Complex; Cornea; Coupled; Couples; Craniofacial Pain; Endothelin; Endothelin A Receptor; Eye; Eye Injuries; Eye diseases; FOS gene; Figs - dietary; Functional disorder; Glaucoma; Goals; Homeostasis; Infection; Lacrimation; Lead; Light; Limb structure; Maintenance; Mass Spectrum Analysis; Mechanics; Mediating; Microinjections; Monitor; Neural Inhibition; Neurons; Nitric Oxide; Nitric Oxide Synthase; Nociception; Nuclear; Ocular Hypertension; Operative Surgical Procedures; Organ; Pain; Parasympathetic Nervous System; Pathway interactions; Peripheral; Photophobia; Physiologic Intraocular Pressure; Process; Property; Proteome; Public Health; Reflex action; Retina; Role; Sampling; Sensory; Sensory Nerve Endings; Source; Staining method; Stains; Stimulus; Structure; Structure of trigeminal ganglion; Symptoms; Synapses; Testing; Thalamic structure; Tissues; Tracer; Trauma; Trigeminal System; Trigeminal nerve structure; Trigeminal subnucleus caudalis; Vision; Visual; Visual Acuity; Visual Pathways; afferent nerve; arm; autonomic reflex; base; brain pathway; design; eye dryness; ganglion cell; indexing; insight; lacrimal; nerve supply; neurophysiology; novel; ocular surface; prevent; public health relevance; receptor; relating to nervous system; research study; response; sensory system; transmission process

DESCRIPTION (provided by applicant): The organization of the eye is well designed to protect the retina, our most sensitive end organ. Environmental challenges to the eye evoke diverse reflexes that maintain ocular blood flow, intraocular pressure, pupillary diameter and lacrimation. Normal ocular reflex function depends on an intact trigeminal sensory system for full expression. Trigeminal nerves supply virtually all tissues of the eye and serve as the afferent limb for many protective reflexes mediated by the parasympathetic nervous system (PaNS). The long-term goal of this project is to determine how trigeminal and PaNS pathways interact to mediate ocular homeostasis and reflex lacrimation. Trigeminal sensory nerves that supply the eye terminate in two spatially distinct regions of the lower brainstem, trigeminal interpolaris/caudalis transition (Vi/Vc) and trigeminal caudalis/cervical cord junction (Vc/C1) regions. Although much is known about corneal sensory nerves, little is known about trigeminal nerves that supply intraocular tissues. To aid this effort, we developed a novel non-invasive stimulus paradigm that uses bright light. Bright light caused lacrimation and selectively excited intraocular trigeminal nerves and, in turn, second-order neurons at the Vc/C1 junction. Bright light-evoked Vc/C1 neural activity required a relay in accessory visual pathways, increased PaNS outflow to the eye and transmission through the trigeminal ganglion. To better understand how intraocular trigeminal nerves contribute to PaNS-mediated reflexes we will test the overarching hypothesis that intraocular and ocular surface trigeminal nerves project to common second-order neurons in two spatially distinct trigeminal brainstem regions that serve different aspects of ocular homeostasis. Aim 1 determines the peripheral mechanism(s) in the eye that couples bright light to trigeminal brainstem activity using single neuron recording and manipulations that alter ocular blood flow and PaNS transmitter release. Aim 2 determines the properties and efferent projections of light-responsive neurons at the Vi/Vc transition region, since currently only Vc/C1 neurons have been tested for bright light sensitivity. Aim 3 determines the roles of the superior salivatory and Edinger-Westphal nuclei on bright light-evoked trigeminal brainstem neural responses, the main sources of PaNS outflow to the eye that affect blood flow to different ocular tissues. Tear volume and composition is monitored as an index of PaNS-mediated reflex activity. This project will provide new information on the role of trigeminal sensory nerves and CNS mechanisms that mediate ocular protective reflexes. Disruption of trigeminal-PaNS relations may contribute to symptoms in diverse conditions as dry eye disease, glaucoma and ocular hypertension that can lead to loss of visual acuity and cause discomfort. PUBLIC HEALTH RELEVANCE: Maintenance of visual function after trauma, surgery or infection requires the coordinated effort of several homeostatic reflexes. Determining how the trigeminal nerve interacts with the autonomic nervous system after ocular injury may help understand how brain pathways contribute to ocular homeostasis.

描述（由申请人提供）：眼睛的组织设计良好，以保护视网膜，我们最敏感的最终器官。对眼睛的环境挑战引起维持眼血流、眼内压、瞳孔直径和流泪的各种反射。正常的眼反射功能依赖于完整的三叉神经感觉系统的充分表达。三叉神经几乎供应眼睛的所有组织，并作为副交感神经系统（PaNS）介导的许多保护性反射的传入分支。本项目的长期目标是确定三叉神经和PaNS通路如何相互作用以介导眼内稳态和反射性流泪。供应眼睛的三叉神经感觉神经终止于下脑干的两个空间上不同的区域，三叉神经极间/尾侧过渡（Vi/Vc）和三叉神经尾侧/颈髓连接（Vc/C1）区域。虽然对角膜感觉神经了解很多，但对供应眼内组织的三叉神经知之甚少。为了帮助这一努力，我们开发了一种新的非侵入性刺激范式，使用明亮的光。明亮的光线引起流泪和选择性兴奋眼内三叉神经，反过来，二级神经元在Vc/C1交界处。明亮的光诱发的Vc/C1神经活动需要在辅助视觉通路的中继，增加PaNS流出到眼睛和传输通过三叉神经节。为了更好地了解眼内三叉神经如何促进PaNS介导的反射，我们将测试总体假设，即眼内和眼表三叉神经投射到两个空间上不同的三叉神经脑干区域中的共同二级神经元，这些区域服务于眼内稳态的不同方面。目的1使用单神经元记录和改变眼血流量和PaNS递质释放的操作来确定将强光与三叉神经脑干活动耦合的眼睛外周机制。目的2确定Vi/Vc过渡区的光响应神经元的属性和传出投射，因为目前只有Vc/C1神经元已被测试为明亮的光敏感性。目的3确定上级流涎核和Edinger-Westphal核在明亮光诱发的三叉神经脑干神经反应中的作用，这是PaNS流出到眼睛的主要来源，影响到不同眼部组织的血流。监测泪液体积和组成作为PaNS介导的反射活性的指标。这个项目将提供新的信息三叉神经感觉神经和中枢神经系统的作用，介导眼睛的保护性反射。三叉神经-PaNS关系的破坏可能导致不同病症的症状，如干眼病、青光眼和高眼压，可导致视力丧失并引起不适。 公共卫生关系：在创伤、手术或感染后维持视觉功能需要几种稳态反射的协调努力。确定眼损伤后三叉神经如何与自主神经系统相互作用可能有助于理解大脑通路如何有助于眼内稳态。