Functional neuroanatomy of the pre-Botzinger complex

描述(申请人提供)：呼吸依赖于几个肌肉群在空间和时间上协调的收缩和放松，这些肌肉群控制着肺充气和呼吸道直径。一个神经元网络也控制着心输出量和区域血流量，这就是这些运动神经流出的原因。这个网络在很大程度上局限于脑干，其完整性对于血气平衡和将氧气输送到有代谢需求的组织至关重要。脑干呼吸神经元中相对较小的一部分似乎致力于产生呼吸节律，而呼吸网络的其余部分被称为模式生成器，负责阐述各种运动流出。本项目重点研究延髓腹外侧网状结构的一部分，其中包含被认为对呼吸节律的形成及其由中枢化学感受器和缺氧控制至关重要的神经元(前Botzinger复合体；前BotC)。Pre-BotC的细胞成分在很大程度上是未知的，除了它们在体外新生啮齿动物中的一些神经生理特性。本项目的目的是研究成年啮齿动物BotC前C区的功能神经解剖学，以进一步了解呼吸节律产生和中枢化学接收的细胞和分子基础。这一目标将通过各种神经生理学和神经解剖学实验来实现，这些实验旨在确定神经元的表型(主要的肌力递质、选定的多肽、受体和通道)和连接，其放电模式和位置将得到充分表征。呼吸网络是大脑功能维持生命的一个重要方面。这项拟议的工作将有助于理解其基本的细胞组织。这项工作代表了改善许多心肺疾病的医疗管理最终可能基于的基础。这些病理状态包括睡眠呼吸暂停及其心血管后果、新生儿心动过缓低氧综合征、婴儿死亡综合征，可能还有各种肺部疾病、高血压和充血性心力衰竭。

DESCRIPTION (provided by applicant): Respiration relies on the spatially and temporally coordinated contraction and relaxation of several muscle groups that control lung inflation and airway diameter. A network of neurons that also controls the cardiac output and regional blood flows elaborates these motor outflows. This network is largely confined to the brainstem and its integrity is essential for blood gas homeostasis and to match oxygen delivery to tissues with metabolic demand. A relatively small fraction of the brainstem respiratory neurons seems dedicated to generating the breathing rhythm whereas the rest of the respiratory network, called the pattern generator, elaborates the various motor outflows. The present project focuses on a portion of the ventrolateral medullary reticular formation that contains neurons (the pre-Botzinger complex; pre-BotC) thought to be essential for the genesis of the respiratory rhythm and its control by central chemoreceptors and hypoxia. The cellular components of the pre-BotC are largely uncharacterized save for some of their neurophysiological properties in neonate rodents in vitro. The goal of the present project is to examine the functional neuroanatomy of the region of the pre-BotC in the adult rodent to further understand the cellular and molecular basis of respiratory rhythm generation and central chemoreception. This objective will be accomplished using a variety of neurophysiological and neuroanatomical experiments designed to identify the phenotype (main inotropic transmitter, selected peptides, receptors and channels) and connectivity of neurons whose discharge pattern and location will be fully characterized. The respiratory network is an essential life-sustaining aspect of brain function. The proposed work will contribute to understanding its basic cellular organization. The work represents the foundation upon which improved medical management of many cardiorespiratory pathologies may be eventually based. These pathological states include sleep apnea and its cardiovascular consequences, the bradycardic hypoxic syndrome of the neonate, infant death syndrome and, possibly, various pulmonary diseases, hypertension and congestive heart failure.