Type
Text
Type
Dissertation
Advisor
Collins, William | Solomon, Irene C | Fontanini, Alfredo | Butera, Robert.
Date
2015-08-01
Keywords
Neurosciences | Computational Neuroscience, Hypoglossal, Motoneuron, Neuronal Plasticity, Serotonin
Department
Department of Neuroscience.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76578
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
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 Ca2+ levels, which regulate neural excitability through Ca2+-gated-K+ channels. Here, short-term, long-term, and intracellular Ca2+ 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 Ca2+ response to 5-HT is likely driven by two separate effects: a reduction in Ca2+ influx from the membrane and a concomitant release of Ca2+ 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. | 116 pages
Recommended Citation
Horn, Kyle Graham, "Exploring the Role of Serotonin on Hypoglossal Motoneuron Excitability and Plasticity Through Postnatal Development Via Mathematical Models" (2015). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2472.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2472