Control of Breathing in Vertebrates

充足的氧气供应对所有脊椎动物的所有组织的生存都很重要，但对心脏和大脑等能量需求较高的组织尤为关键。低氧应激(低氧)(环境引起的，如海拔、洞穴和氧气贫乏的水域，或新陈代谢引起的，如运动、消化和繁殖)推动了遇到这些条件的动物的新适应的进化。耐受低氧的关键是使氧气供应与氧气需求相匹配。在调节氧气供应的过程中，第一步是通风，我研究项目的一个目标是确定为什么动物在不同的条件下(休息、睡眠、运动、海拔、休眠、冬眠、潜水等)会有这样的呼吸方式。呼吸是所有大型多细胞生物体进行气体交换所必需的，但呼吸节律产生的机制基础以及基本节律如何被修改以满足不断变化的需求的方式还没有完全被理解。我们也不完全了解气体传输级联中在大气和线粒体之间移动O2和CO2的其他步骤是如何调节和整合的，以满足不同环境中不断变化的需求。这些步骤包括通过鳃/肺扩散气体，通过心脏泵送氧气在血液中的运输，血液容纳氧气的能力，以及氧气从血液扩散到组织中。所有这些步骤都受到外周感觉反馈和下行输入的相互作用，这些输入与运动、唤醒状态(如睡眠、休眠和冬眠)和体温的变化有关。通过研究这一级联调控步骤的机制基础，我们的工作提供了对生命最重要的过程之一气体交换的发育(表型)和进化(遗传型)可塑性的洞察。这个方程式还有另一面。在低氧条件下，可以通过增加供应和抑制需求来满足匹配的氧气供需。人们对缺氧代谢抑制的机制基础以及在氧气供应不断变化的情况下如何修改它，以及如何协调增加供应和减少需求之间的平衡，了解得更少。我和我的学生们希望以物种差异(进化史)、发育变化(个体发生学)和遗传操作为工具，确定代谢供需匹配机制是如何通过进化来塑造的，以满足生活在不同环境中、具有不同生活史的脊椎动物的需求。

An adequate supply of oxygen is important for the survival of all tissues in all vertebrates, but is especially critical for tissues with high energy demands such as heart and brain. Hypoxic stress (low oxygen) (environmentally induced such as at altitude, in burrows and in O2 poor waters, or metabolically induced such as by exercise, digestion and reproduction) has driven the evolution of novel adaptations in animals that encounter such conditions. The key to tolerating hypoxia is to match O2 supply to O2 demand. The first step in the process of regulating O2 supply, is ventilation, and one goal of my research program is to determine why animals breathe the way they do under different conditions (at rest, sleep, exercise, altitude, dormancy, hibernation, diving, etc.). Breathing is essential for gas exchange in all large, multicellular organisms, but the mechanistic basis of respiratory rhythm generation and the manner in which the basic rhythm is modified to meet changing demands are not fully understood. We also don't fully understand how the other steps in the gas transport cascade that move O2 and CO2 between the atmosphere and the mitochondria are regulated and integrated to meet fluctuating demands in different environments. These steps include the diffusion of gases across the gills/lungs, the transport of O2 in the blood by the pumping of the heart, the capacity of blood to hold O2, and the diffusion of O2 from the blood into the tissues. All of these steps are modulated by the interaction of peripheral sensory feedback and such descending inputs as those associated with locomotion, changes in arousal state (such as sleep, dormancy and hibernation) and body temperature. By investigating the mechanistic basis of the regulatory steps in this cascade, our work provides insight into the developmental (phenotypic) and evolutionary (genotypic) plasticity of one of the most essential process for life; gas exchange. There is also another side to this equation. Matching oxygen supply and demand can be met under hypoxic conditions not only by increasing supply but also by suppressing demand. The mechanistic basis of hypoxic metabolic suppression and the manner in which it is modified in the face of changing oxygen supply are even less well understood, as is the manner in which the balance between increasing supply versus reducing demand is orchestrated. Using species differences (phylogeny), developmental changes (ontogeny) and genetic manipulations as tools, my students and I hope to determine the ways in which the mechanisms matching metabolic supply and demand have been shaped by evolution to meet the demands of vertebrates with varied life histories living in different environments.