Neural Circuitry of Upper Airway Respiratory Plasticity: Identifying the Neural Circuitry Underlying Long-term Facilitation of Inspiratory Genioglossus Motor Output
Year: 2019
Type: dissertation
Abstract: The respiratory system is highly adaptive and can change its behaviour to provide protective responses in face of repeated respiratory challenges. Elucidating the role of how neurons and neural circuits mediate these responses can open new treatments for those that cannot adapt. Respiratory long-term facilitation (LTF) is one form of adaptation that can increase genioglossus motor output, potentially providing a means to mitigate respiratory disorders such as obstructive sleep apnea. I examined the neural circuitry that underlies this form of respiratory motor plasticity and I identified: (1) the neural circuit that mediates respiratory LTF of inspiratory genioglossus motor output, (2) a novel trigger that elicits LTF without directly or indirectly modulating the respiratory feedback systems, and (3) the neurotransmitter(s) that are essential to the manifestation of respiratory motor plasticity of genioglossus motor output. Using tract-tracing, immunohistochemical and pharmacological approaches, I have identified a tripartite circuit connecting the nucleus tractus solitarius (NTS), the locus coeruleus (LC), and the hypoglossal motor nuclei (XII) that are individually critical to the elicitation of LTF. I also employed a series of optogenetic approaches to identify the LC as a trigger that can elicit LTF following intermittent stimulation of the LC alone. Lastly, I identified noradrenaline, released by the LC and acting on α1-adrenergic receptors at the hypoglossal motor nuclei, to be the key neurotransmitter-receptor system that gates the expression of respiratory motor plasticity. These findings provide direction and novel therapeutic targets to treat respiratory disorders such as obstructive sleep apnea.
Source: TSpace (University of Toronto)
Author: Simon Lui
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3147060299