John Horner's journey into sleep research began in the early 1990s as a PhD student at the University of London, one of the UK's first sleep laboratories. He was attracted to the University of Toronto (U of T) for a postdoctoral fellowship under clinician-scientist Eliot Phillipson, who had established one of North America's first human sleep labs in 1978 to focus on breathing disturbances.
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In 1997, following a second postdoctoral fellowship at the University of Pennsylvania, Horner joined the U of T faculty. His primary goal was to create new tools for more effectively studying sleep and breathing, as prior models mostly simulated sleep-like behavior. Horner emphasized the importance of studying natural sleep, aiming to conduct fundamental neuroscience investigations into the circuits controlling the muscles that facilitate breathing.
The Horner lab made significant advancements in identifying key brain chemicals and receptors that modulate respiratory muscle activity during sleep. In 2006, they first identified the neurotransmitter noradrenaline as crucial for activating the tongue muscle during wakefulness and various sleep phases.
The tongue plays a vital role in speech and swallowing, but Horner pointed out its significance as the largest upper airway muscle responsible for maintaining airflow to the lungs. During rapid eye movement (REM) sleep, when most dreaming occurs, noradrenaline levels in the brain decrease, causing a loss of muscle tone in the tongue and leading to potential breathing difficulties for some individuals.
In 2013, the lab published a groundbreaking finding that a family of proteins known as muscarinic receptors suppresses tongue movement during REM sleep. Blocking these receptors with a drug was shown to significantly activate the tongue muscle.
These discoveries from the Horner lab identified two critical factors contributing to sleep apnea: the loss of a noradrenaline