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    Serotonergic And Hypocretinergic Systems Modulate Ventilation And Hypercapnic Ventilatory Responses

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    Author
    Corcoran, Andrea E.
    Keyword
    Physiology
    Neurosciences
    Metadata
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    URI
    http://hdl.handle.net/11122/9005
    Abstract
    Serotonergic (5-HT) cells of the medullary raphe are putative central chemoreceptors, one of multiple chemoreceptive sites in the brainstem that interact to produce the respiratory chemoreflex. This role is debated, and the importance of 5-HT neurons as chemoreceptors in relatively intact systems is unclear. The main focus of this dissertation is to provide further physiological evidence for the involvement and modulation of 5-HT neurons in CO2 chemosensitivity. This is of interest as a large number of Sudden Infant Death Syndrome (SIDS) cases report dysfunction in the 5-HT system, and CO2 may be an exogenous stressor leading to SIDS when in combination with this underlying vulnerability. Also, since SIDS occurs primarily during sleep, I also focus on the potential functional interaction between the 5-HT and hypocretinergic systems, as hypocretins play a role in arousal and also potentially in chemosensitivity. I confirm the hypothesis that the serotonergic and hypocretinergic systems modulate ventilation and hypercapnic ventilatory responses. Using the in situ preparation derived from juvenile rats and the in vitro medullary slice preparation from mice, I verify that 5-HT neurons are critical in generating a response to CO2, primarily via facilitation of the respiratory rhythm through 5-HT2 receptors. I also find evidence to support the hypothesis that hypocretins play a significant role in the neuroventilatory response to CO2 through activation of hypocretin receptors type 1. By comparing results from rhythmic medullary slice preparations from wildtype (normal 5-HT function) and Lmx1bf/f/p (lack central 5-HT neurons) neonatal mice, I attempt to identify whether changes in hypoglossal nerve output in response to acidosis are affected by hypocretin receptors, and whether this is dependent on the presence of 5-HT neurons. Frequency results from such studies are inconclusive; however, hypocretins do appear to mediate the burst duration response via serotonergic mechanisms. I also find that hypocretins facilitate baseline neural ventilatory output in part through 5-HT neurons. Thus, both the 5-HT and hypocretinergic systems are involved in modulating ventilation and hypercapnic ventilatory responses.
    Description
    Dissertation (Ph.D.) University of Alaska Fairbanks, 2009
    Date
    2009
    Type
    Dissertation
    Collections
    Biological Sciences

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