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Exploring the Role of Serotonin on Hypoglossal Motoneuron Excitability and Plasticity Through Postnatal Development Via Mathematical Models

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dc.contributor.advisor Solomon, Irene C en_US
dc.contributor.author Horn, Kyle Graham en_US
dc.contributor.other Department of Neuroscience en_US
dc.date.accessioned 2017-09-20T16:50:42Z
dc.date.available 2017-09-20T16:50:42Z
dc.date.issued 2015-08-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/76578 en_US
dc.description 116 pgs en_US
dc.description.abstract Neuronal plasticity is a key facet of neurons throughout the central and peripheral nervous system. Unlike most forms of plasticity, however, dysfunctions in respiratory motoneuron plasticity can be fatal. With respect to hypoxic conditions, hypoglossal motoneurons (HMs), which participate in a variety of upper airway behaviors, are considered critical for maintaining upper airway patency. Failure in these neurons can disfacilitate the tongue, rendering an obstruction in the upper airway. This can exacerbate hypoxic conditions, and may potentially contribute to sudden infant death syndrome (SIDS) and obstructive sleep apnea (OSA). Serotonin (5-HT) affects HM excitability through a wide variety of mechanisms, and the density of 5-HT receptors has been shown to change during postnatal development. 5-HT is known to participate in the initiation of both short- and long-term hypoxic responses in the isolated HM, with repeated bouts of either hypoxia or 5-HT evoking a persistent increase in HM excitability known as long-term facilitation (LTF). In addition, 5-HT modulates intracellular Ca<super>2+</super> levels, which regulate neural excitability through Ca<super>2+</super>-gated-K<super>+</super> channels. Here, short-term, long-term, and intracellular Ca<super>2+</super> responses to simulated hypoxic bouts are investigated via three developmentally distinct 5-HT sensitive HM computational models: neonatal (P3-P5), juvenile (P7-P12), and adult (>P21). Results from model simulations demonstrate that (1) the intracellular Ca<super>2+</super> response to 5-HT is likely driven by two separate effects: a reduction in Ca<super>2+</super> influx from the membrane and a concomitant release of Ca<super>2+</super> from intracellular stores, (2) the 5-HT1A receptor is implicated primarily in the short-term hypoxic response while the 5-HT2 receptor plays a greater role in the long-term response, (3) LTF initiation is governed by PKC activation and maintenance derives from MAPK cascade bistability, and (4) the juvenile HM model exhibits a blunted capability to undergo LTF compared to the neonatal and adult HM models, which may play a role in age-specific pathologies. Finally, a mathematical reduction over these models is implemented to identify the fundamental requirements to derive such behavior in neural systems in general. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Neurosciences en_US
dc.subject.other Computational Neuroscience, Hypoglossal, Motoneuron, Neuronal Plasticity, Serotonin en_US
dc.title Exploring the Role of Serotonin on Hypoglossal Motoneuron Excitability and Plasticity Through Postnatal Development Via Mathematical Models en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Collins, William en_US
dc.contributor.committeemember Fontanini, Alfredo en_US
dc.contributor.committeemember Butera, Robert en_US


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