Mechanisms of respiratory-related rhythmic motor activity and plasticity in the avian brain stem

禽类脑干呼吸相关节律性运动活动和可塑性的机制

• 批准号: 8812709
• 负责人: Jason Quinn Pilarski
• 金额: $ 36.26万
• 依托单位: IDAHO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8812709
• 关键词: Abdomen; Acute; Address; Adult; Air; Behavior; Biological Models; Biological Neural Networks; Birds; Brain Stem; Breathing; Cations; Cell Nucleus; Cells; Cephalic; Chemicals; Chloride Ion; Chlorides; Clinical Treatment; Communication; Coupled; Data; Development; Disease; Embryo; Environment; Equilibrium; Exercise; Experimental Models; Fire - disasters; Funding; Generations; Glossopharyngeal nerve structure; Goals; Health; Hour; Human; Idaho; Image; In Vitro; Individual; Interneurons; Knowledge; Lead; Life; Location; Maintenance; Mammals; Measures; Mediating; Mind; Modeling; Modification; Morbidity - disease rate; Motor; Motor Activity; Motor Neurons; Movement; Muscle; Nervous system structure; Network-based; Neurons; Neurotransmitters; Nicotine; Nicotinic Receptors; Output; Pacemakers; Pathway interactions; Pattern; Pattern Formation; Pharmacology; Phase; Phenotype; Physiology; Preparation; Recovery; Research; Resistance; Respiration; Rest; Role; Science; Shapes; Signal Transduction; Sodium Channel; Spinal Cord; Staging; Stress; Structure; Students; Support System; Synapses; Techniques; Testing; Time; Training; Universities; Vertebrates; base; career; central pattern generator; clinically relevant; developmental neurobiology; developmental plasticity; experience; expiration; extracellular; fetal tobacco exposure; gamma-Aminobutyric Acid; graduate student; hatching; in vitro activity; in vivo; interest; mortality; neonate; neurogenesis; neuropathology; neurotransmission; novel; prenatal; programs; public health relevance; receptor function; relating to nervous system; respiratory; response; undergraduate student; zebra finch

DESCRIPTION (provided by applicant): The long term goal of our research team is to understand how brain stem motor circuits that control life sustaining autonomous breathing patterns develop, mature and maintain rhythmic neural activity. It is also relevant to determine how these circuits respond to abnormal environments and stress. This project proposes to use a new experimental model system to explore the location(s), synaptic physiology, and plasticity of breathing-related central pattern generators (CPGs) in the isolated Zebra Finch brain stem during early development. The avian embryonic model is uniquely tractable for experimental manipulation and provides unparalleled access to central neuronal networks throughout prenatal development. We will use anatomical techniques, nerve cell activities, and pharmacology to test our hypotheses in the context of understanding normal breathing behaviors and breathing-related neuropathologies in which the modification or loss of brain stem structures that control normal rhythm and motor patterns can lead to increased morbidity and mortality in neonates and adults. Importantly, funds from this proposal will introduce students to Biomedically-based research at Idaho State University (ISU) using hands-on lab experiences and focused individual training in a variety of professional and scientific practices. We seek to address three key aspects associated with the field of developmental neurobiology and the control of breathing: 1. Identification of spatially separate respiratory-related brain stem CPGs. Aim 1 will test the role of the avian nucleus paraambiguus (PAm) and the retroambiguus (RAm) in the neurogenesis of automatic breathing rhythms. Historically, in vitro studies have focused on the inspiratory phase. Yet, the breathing cycle involves both inspiration and expiration. Since birds employ active inspiration and active expiration, even at rest, we hypothesize that avian embryos at the internal hatching stage (i.e., when continuous air-breathing begins) generate breathing rhythms with two independent yet coupled CPGs, similar to the situation in exercising humans when high levels of ventilatory drive is necessary. 2. Mechanisms of burst generation and pattern formation in the avian brain stem. Aim 2 will test the hypothesis that respiratory-related CPG behavior in birds is critically dependent on inhibitory synaptic input, similar to many network-based locomotor CPG circuits. Specifically, we hypothesize spontaneous rhythms will be critically dependent on chloride-mediated neurotransmission as a mechanism to control duty cycles for breathing pattern. As an alternate hypothesis, we will test the role of endogenous pacemaker mechanisms in the maintenance and shape of respiratory-related CPG output.3. Mechanisms of homeostatic/developmental plasticity in the breathing-related brain stem. Aim 3 will test how persistent embryonic manipulations of rhythmic electrical activity with and without manipulations of specific neurotransmitters may alter the developmental expression of CPG behavior as well as the phenotype of neurotransmitter systems that support breathing.

描述（由申请人提供）：我们研究团队的长期目标是了解控制生命维持自主呼吸模式的脑干运动回路如何发育、成熟和维持节律性神经活动。确定这些电路如何响应异常环境和压力也很重要。该项目拟使用一种新的实验模型系统来探索斑胸草雀离体脑干早期发育过程中与呼吸相关的中枢模式发生器（CPG）的位置、突触生理学和可塑性。禽类胚胎模型具有独特的易操作性，易于实验操作，并在整个产前发育过程中提供了无与伦比的中枢神经网络通道。我们将使用解剖技术、神经细胞活动和药理学在理解正常呼吸行为和呼吸相关神经病理学的背景下检验我们的假设，其中控制正常节律和运动模式的脑干结构的改变或丧失可能导致呼吸增加新生儿和成人的发病率和死亡率。重要的是，该提案的资金将向学生介绍爱达荷州立大学 (ISU) 的生物医学研究，利用实验室实践经验和各种专业和科学实践的集中个人培训。我们寻求解决与发育神经生物学和呼吸控制领域相关的三个关键问题： 1. 识别空间上独立的呼吸相关脑干 CPG。目标 1 将测试鸟类副疑核 (PAm) 和后疑核 (RAm) 在自动呼吸节律的神经发生中的作用。从历史上看，体外研究主要集中在吸气相。然而，呼吸循环涉及吸气和呼气。由于鸟类即使在休息时也会采用主动吸气和主动呼气，因此我们假设鸟类胚胎在内部孵化阶段（即开始连续呼吸空气时）会产生具有两个独立但耦合的 CPG 的呼吸节律，类似于人类运动时的情况当需要高水平的通气驱动时。 2. 禽类脑干爆发产生和模式形成的机制。目标 2 将检验以下假设：鸟类与呼吸相关的 CPG 行为严重依赖于抑制性突触输入，这与许多鸟类类似。 基于网络的运动 CPG 电路。具体来说，我们假设自发节律将严重依赖于氯介导的神经传递作为控制呼吸模式占空比的机制。作为替代假设，我们将测试内源性起搏器机制在呼吸相关 CPG 输出的维持和形状中的作用。3。呼吸相关脑干的稳态/发育可塑性机制。目标 3 将测试在有或没有特定神经递质操作的情况下对节律性电活动的持续胚胎操作可能如何改变 CPG 行为的发育表达以及支持呼吸的神经递质系统的表型。