Functional neuroanatomy of the pre-Botzinger complex

描述（由申请人提供）：呼吸依赖于控制肺膨胀和气道直径的几个肌肉群在空间和时间上协调的收缩和放松。控制心输出量和局部血流的神经元网络详细说明了这些运动流出。该网络主要局限于脑干，其完整性对于血液气体稳态和代谢需求组织的氧气输送至关重要。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奏，而呼吸网络的其余部分，称为模式发生器，详细说明各种运动流出。目前的研究重点是腹外侧髓网状结构的一部分，该部分包含神经元（pre-Botzinger复合体；pre-BotC），被认为是呼吸节律的发生及其由中央化学受体和缺氧控制的必要条件。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。本项目的目标是检查成年啮齿动物前botc区域的功能神经解剖学，以进一步了解呼吸节律产生和中枢化学接受的细胞和分子基础。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、选定的肽、受体和通道）和连通性，这些神经元的放电模式和位置将得到充分表征。呼吸网络是维持大脑功能的一个重要方面。所提出的工作将有助于了解其基本细胞组织。这项工作代表了许多心肺疾病的改进医疗管理可能最终基于的基础。这些病理状态包括睡眠呼吸暂停及其心血管后果、新生儿心动过缓缺氧综合征、婴儿死亡综合征以及可能的各种肺部疾病、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.