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.
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