Dissertation/Thesis Abstract

Serotonin Signaling in the Nucleus Tractus Solitarius Modulates the Laryngeal Chemoreflex: Implications for Sudden Infant Death Syndrome
by Donnelly, William T., Ph.D., Dartmouth College, 2016, 105; 10145494
Abstract (Summary)

Sudden infant death syndrome (SIDS) occurs when a sleeping infant experiences a challenge to cardiorespiratory homeostasis which it fails to overcome. Analyses of brain tissue from SIDS cases from around the world consistently show abnormalities in the brainstem serotonin systems. These include increased numbers of neurons that test positive for serotonergic markers, but have an immature phenotype, reduced brain tissue serotonin concentrations and decreased serotonin receptor binding in projection sites important to cardiorespiratory homeostasis, including the nucleus of the solitary tract (NTS). The NTS is of particular interest in the pathophysiology of SIDS because it is the integration center for afferent projections involved in eliciting several apnea-inducing reflexes long suspected of contributing to SIDS. The laryngeal chemoreflex (LCR), an airway protective reflex which is initiated when water, acidic solutions, or low [Cl-] solutions activate chemoreceptors in the larynx, is one such reflex. In infants, inhibitory reflex responses to hypoxia (apnea, bradycardia, decreased metabolic activity) that are adaptive for a fetal environment that precludes the possibility of the fetus acquiring more oxygen by increasing breathing, persist for some time into the postnatal period. Therefore, hypoxia resulting from apnea caused by the LCR can result in a cataclysmic downward spiral of apnea, followed by increasing hypoxic inhibition of respiration, which ultimately leads to SIDS. We hypothesized that increasing serotonin signaling in the brainstems of rat pups would shorten the apnea and respiratory disruption caused by eliciting the LCR. We have shown that both intracisternal injections of serotonin, and microinjections of serotonin into the caudal NTS, dramatically shorten the LCR. This effect is also seen after microinjection into the NTS of the 5-HT3 specific agonist CPG. Chemical stimulation by microinjection of AMPA of neurons in the raphe obscurus, some of which send serotonergic projections to the NTS, also shortens the LCR, but this effect is blocked by prior injection of a 5-HT3 antagonist in the NTS. Our work suggests that serotonergic projections to the NTS from the caudal raphe may play an important role in limiting the duration of apnea following inhibitory reflexes like the LCR and in the subsequent restoration of eupnea.

Indexing (document details)
Advisor: Leiter, James C.
Commitee: Andresen, Michael C., Bartlett, Donald, Darnall, Robert A.
School: Dartmouth College
Department: Physiology
School Location: United States -- New Hampshire
Source: DAI-B 77/12(E), Dissertation Abstracts International
Subjects: Neurosciences, Physiology, Developmental biology
Keywords: 5-HT3, Chemoreflex, Laryngeal, Laryngeal chemoreflex, Nucleus of the solitary tract, Serotonin
Publication Number: 10145494
ISBN: 978-1-369-01003-9
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