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展，成熟和维持有节奏的神经活动。它也与确定这些电路如何响应异常环境和压力有关。本项目拟利用一种新的实验模型系统来探索离体斑胸草雀脑干发育早期与呼吸相关的中枢模式发生器（CPGs）的位置、突触生理学和可塑性。鸟类胚胎模型是唯一易于实验操作，并提供了无与伦比的访问中央神经元网络在整个产前发育。我们将使用解剖学技术，神经细胞活动和药理学来测试我们的假设，了解正常的呼吸行为和呼吸相关的神经病理学，其中控制正常节律和运动模式的脑干结构的修改或丢失可能导致新生儿和成人发病率和死亡率增加。重要的是，该提案的资金将向学生介绍爱达荷州州立大学（ISU）的生物医学研究，使用实践实验室经验和各种专业和科学实践的重点个人培训。我们试图解决与发育神经生物学和呼吸控制领域相关的三个关键方面：1。空间分离的脑干相关CPG的识别。目的1：研究鸟类疑旁核（PAm）和疑后核（RAm）在自主呼吸节律发生中的作用。从历史上看，体外研究主要集中在吸气阶段。然而，呼吸周期包括吸气和呼气。由于鸟类即使在休息时也会进行主动吸气和主动呼气，因此我们假设处于内部孵化阶段的鸟类胚胎（即，当连续的空气呼吸开始时）产生具有两个独立但耦合的CPG的呼吸节律，类似于当需要高水平的呼吸驱动时锻炼人的情况。2.鸟类脑干内爆发产生与图案形成之机制。目的2将检验这一假设，即鸟类中与行为相关的CPG行为严重依赖于抑制性突触输入，类似于许多 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化物介导的神经传递，作为控制呼吸模式占空比的机制。作为一个替代假设，我们将测试内源性起搏机制在维持和形成与心脏相关的CPG输出中的作用。呼吸相关脑干的稳态/发育可塑性机制。目的3将测试持续的胚胎操作的节律性电活动与特定的神经递质的操作和不操作可能会改变CPG行为的发育表达，以及支持呼吸的神经递质系统的表型。