| The overall goal of this study is to increase our understanding of the neural control of respiration at several hierarchical levels. The respiratory rhythm in mammals is generated in the lower brainstem where groups of neurons, which comprise the respiratory central pattern generator (CPG), interact to produce a motor output that controls breathing. The pre-Botzinger complex (pre-BotC) located in the medullary ventrolateral respiratory column (VRC) is the putative source of rhythmic inspiratory activity. Though there has been a substantial push to understand the cellular and network mechanisms operating within the pre-BotC, as well as its interactions with the larger respiratory network, there is still much to be resolved.;Using a dynamic systems approach, a series of computational models were developed to reproduce various experimental data obtained in vitro and in vivoand to generate verifiable predictions. The scale of this modeling work encompasses the interaction of neurons within the pre-BotC, their interactions with several other brainstem compartments representing the core of the mammalian respiratory CPG, and an integration of the respiratory network into a larger control system that includes afferent feedback loops. At each level, I address specific, but related, issues that add to the general understanding of the neural control of respiration. This includes: (i) the characteristic rhythmic bursting behavior observed in the pre-BotC, which was studied at the cellular level with a particular focus on how this behavior impacts inspiratory motor outputs; (ii) interactions between several neural populations in the VRC that produce an alternating motor pattern composed of inspiratory and expiratory phases and how this pattern may be affected by changes in the chemical environment, e.g. during hypercapnia (elevated carbon dioxide) or hypoxia (diminished oxygen); and (iii) the role of afferent feedback to the VRC from the pons and lungs, which was studied in the context of respiratory phase switching mechanisms.;The results of this study were published in several high impact scientific journals and can provide important insights to our understanding of the neural control of breathing. |
