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如何控制维持生命的自主呼吸模式的脑干电路，成熟并保持节奏的神经活动。确定这些电路如何应对异常环境和压力也很重要。该项目建议使用新的实验模型系统来探索在早期发育过程中孤立的斑马鳍脑干中与呼吸相关的中央模式发生器（CPG）的位置和可塑性。鸟类胚胎模型可用于实验性操纵，并在整个产前发育过程中提供无与伦比的中央神经元网络的访问。我们将使用解剖技术，神经细胞活性和药理学在理解正常的呼吸行为和与呼吸有关的神经病理学的背景下测试我们的假设，在这种情况下，控制正常的节奏和运动模式的脑干结构的修饰或丧失会导致新生儿和成人的发病率增加。重要的是，该提案的资金将使用动手实验室经验和专注于各种专业和科学实践的个人培训向学生介绍基于生物医学的研究。我们试图解决与发育神经生物学领域相关的三个关键方面和呼吸的控制：1。鉴定与空间分开的呼吸相关脑干CPG。 AIM 1将测试鸟核Paraambiguus（PAM）和retroambiguus（RAM）在自动呼吸节奏的神经发生中的作用。从历史上看，体外研究集中在灵感阶段。然而，呼吸周期既涉及灵感和到期。由于鸟类采用活跃的灵感和主动到期，即使在静止的情况下，我们假设在内部孵化阶段（即，当连续的空气呼吸开始开始时）在内部孵化阶段（即，当连续的空气呼吸开始时）会产生呼吸节奏，这与两个独立但耦合的CPG相似，类似于当需要高水平的频道驱动驱动器时进行锻炼的情况。 2。禽脑干中爆发产生和模式形成的机制。 AIM 2将检验以下假设：鸟类中与呼吸有关的CpG行为至关重要取决于抑制性突触输入，类似于许多 基于网络的运动CPG电路。具体而言，我们假设自发节奏将严重取决于氯化物介导的神经传递，作为呼吸模式控制占空比的一种机制。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。与呼吸有关的脑干中稳态/发育可塑性的机制。 AIM 3将测试有或没有操纵特定神经递质的节奏电活动的持续性胚胎操纵如何改变CpG行为的发育表达以及支持呼吸的神经递质系统的表型。