Respiratory Pattern Generation Studied in Vitro

体外研究呼吸模式生成

• 批准号: 7249376
• 负责人: JACK L FELDMAN
• 金额: $ 44.4万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7249376
• 关键词: Affect; Age; Apnea; Behavior; Birth; Brain; Breathing; Carbon Dioxide; Central Sleep Apnea; Chromosome Pairing; Complex; Condition; Coughing; Data; Development; Disease; Environmental air flow; Exercise; Figs - dietary; Functional disorder; Generations; Grant; Human; Hypercapnic respiratory failure; Hypoxia; In Vitro; Investigation; Knowledge; Laboratories; Link; Locomotion; Lung; Mammals; Measurable; Modification; Movement; Neonatal; Nervous system structure; Neurons; Outcome; Pacemakers; Pattern; Periodicity; Personal Satisfaction; Physiology; Population; Pregnancy loss; Prematurity of fetus; Preparation; Property; Prophylactic treatment; Reflex action; Respiratory Failure; Respiratory Muscles; Rodent; Site; Sleep; Sleep Apnea Syndromes; Slice; Sneezing; Solutions; Speech; Sudden infant death syndrome; Synapses; System; Testing; Weight Gain; Work; base; design; fly; in utero; neural circuit; neuromechanism; novel; research study; respiratory; voltage

DESCRIPTION (provided by applicant): Breathing movements in mammals start episodically in utero, are continuous at birth, and except for the briefest of pauses, continue without respite. The neural circuits underlying breathing must be wired correctly by birth, and must change on the fly as the lungs and respiratory muscles mature and then age. These circuits must be stable yet responsive to challenges affecting O2, CO2 and pH levels in the body such as exercise, sleep and hypoxia. They must be well coordinated with other movements generating airflow such as speech, and airway reflexes such as cough or sneeze, as well as movements impacting the respiratory muscles and lungs such as locomotion. Longer-lasting disturbances demand adaptive solutions; for example, breathing must be adjusted to accommodate physical changes associated with weight gain and loss, pregnancy or disease. At the core of breathing movements is rhythmicity. Here we propose to determine where and how respiratory rhythm is generated in mammals. In 1991, we proposed two hypotheses: i) The preBotzinger Complex (preBotC) contains the kernel for generating respiratory rhythm, ii) Neurons with pacemaker properties underlie the generation of respiratory rhythm. These hypotheses have been the basis for a large body of work in laboratories worldwide. Recent work suggests two alternative hypotheses: i) The preBotC and preinspiratory (pre-I) neuron population interact to produce respiratory rhythm, ii) A group pacemaker network underlies rhythm generation. This grant proposes experiments that test these hypotheses and reevaluate new hypotheses. We have designed the proposed experiments in such a way that regardless of the their outcome, the data will add substantially and in unique ways to our understanding of neural mechanisms underlying the generation of respiratory rhythm and pattern. Determination of the mechanisms underlying breathing movements is basic to understanding human physiology and the pathophysiology of many diseases. Development of prophylaxis and treatment of such diseases as Sudden Infant Death Syndrome, apnea of prematurity, central alveolar hypoventilation, congenital central hypoventilation syndrome, sleep apnea and other forms of respiratory failure critically depend on such knowledge. Studying a measurable behavior under controlled in vitro conditions permits novel experiments that can reveal important features of the link between synapses/neurons and behavior that may have general applicability in understanding mammalian brain function.

描述（由申请人提供）：哺乳动物中的呼吸运动在子宫内偶发地开始，出生时是连续的，除了最短时间的停顿外，继续没有喘息。呼吸下的神经回路必须通过出生正确连接，并且随着肺部和呼吸肌肉成熟，然后年龄的年龄，必须随时变化。这些电路必须稳定，但要应对影响体内O2，CO2和pH值的挑战，例如运动，睡眠和缺氧。它们必须与其他动作进行良好的协调能力，这些动作产生了诸如语音的气流，以及咳嗽或打喷嚏等气道反射，以及影响呼吸肌肉和肺部（例如运动）的运动。持续的干扰需要自适应解决方案；例如，必须调整呼吸以适应与体重增加和损失，怀孕或疾病相关的身体变化。呼吸运动的核心是节奏。在这里，我们建议确定哺乳动物中呼吸节奏的何处以及如何产生。在1991年，我们提出了两个假设：i）prebotzinger复合物（Prebotc）包含用于产生呼吸节奏的内核，ii）具有起搏器特性的神经元是呼吸节奏产生的基础。这些假设一直是全球实验室大量工作的基础。最近的工作提出了两个替代假设：i）PrebotC和呼吸培训（PER-I）神经元种群相互作用以产生呼吸节奏，ii）组的起搏器网络是节奏生成的基础。该赠款提出了测试这些假设并重新评估新假设的实验。我们设计了提出的实验，以使数据无论结果如何，数据都将大幅度地增加我们对呼吸节奏和模式产生的神经机制的理解。确定呼吸运动的机制是理解人类生理学和许多疾病的病理生理学的基础。预防性的发展和治疗诸如婴儿猝死综合征，早产呼吸暂停，中央肺泡不足衰减，先天性中央中央低衰减综合征，睡眠呼吸呼吸暂停和其他形式的呼吸衰竭等疾病的治疗。研究在受控的体外条件下可测量的行为允许新的实验，这些实验可以揭示突触/神经元与行为之间的联系的重要特征，这些特征可能在理解哺乳动物脑功能方面具有一般适用性。