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Principal Investigator: Alyssa Huff
Organization: SEATTLE CHILDREN'S HOSPITAL
Fiscal Year: 2024
Award: $78,892
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
Coordination of breathing with postinspiratory behaviors such as swallowing and laryngeal adduction is
essential to health. Dysregulation of laryngeal activity during postinspiration and swallow occurs in many
neurological and breathing-related disorders, such as obstructive sleep apnea, and can increase the risk of
disordered swallow (dysphagia) and aspiration. Dysphagia is a major problem in patients with these diseases,
and there are currently no treatments to cure or prevent dysphagia. This deficit is due in part to the lack of
studies on coordination of breathing with laryngeal function of postinspiration and swallow. The recently
described brainstem Postinspiratory Complex (PiCo) is thought to control postinspiration, yet its role in other
laryngeal behaviors has not been studied. We test a fundamentally new hypothesis that excitatory medullary
transmission from PiCo to the swallow pattern generator plays a role in swallow-related postinspiratory
behavior. Our goals is to define the role of PiCo in postinspiratory laryngeal activity and swallow, and
investigate potential coordination between the dorsal swallow group (DSG) and the ventral respiratory group
(VRG). Based on preliminary data, we hypothesize that PiCo is a hub for both postinspiratory activity and
swallowing, and has connections to the presumed swallow pattern generator in the nucleus tractus solitarius
(nTS). We believe PiCo plays a role in swallow-related rhythmic activities which includes the nTS as the
presumed swallow rhythm generator with projections to ventral respiratory centers. We use two in-vivo
preparation: anesthetized and alert mouse combined with electrophysiology, novel optogenetics and
Neuropixel recordings to test these hypotheses. We predict neural coordination of PiCo activity with respiratory
and non-respiratory centers is similar between anesthetized and unanesthetized preparations. Investigating
PiCo in an alert animal is important for characterizing the natural behaviors of swallow and laryngeal
postinspiratory activity in a translational manner.
Terms: <Anesthesia><Anesthesia procedures><Animals><Behavior><Behavioral><Brain Stem><Brainstem><Breathing><Cause of Death><Cell Nucleus><Complex><Coughing><Cyclicity><Data><Deglutition><Deglutition Disorders><Disease><Disorder><Dorsal><Dysphagia><Electrophysiology><Electrophysiology (science)><Goals><Health><Hydrogen Oxide><Implant><Individual><Injections><Laryngeal><Larynx><Larynx Head and Neck><Lung><Lung Respiratory System><Mice><Mice Mammals><Murine><Mus><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurocyte><Neurologic><Neurologic Disorders><Neurological><Neurological Disorders><Neurons><Neurophysiology / Electrophysiology><Nucleus><Obstructive Sleep Apnea><Oral><Patients><Pattern><Periodicity><Phase><Plethysmography><Pneumonia><Preparation><Property><Respiration><Respiratory Aspiration><Respiratory Center><Respiratory Inspiration><Rhythmicity><Risk><Role><Swallowing><Swallowing Disorders><Syndrome, Sleep Apnea, Obstructive><Techniques><Testing><Transmission><Water><adduct><aspirate><disease risk><disorder risk><electrophysiological><expiration><in vivo><inspiration><neural><neural circuit><neural circuitry><neurocircuitry><neurological disease><neuronal><novel><optogenetics><preBotzinger complex><preparations><prevent><preventing><pulmonary><respiratory><respiratory mechanism><response><social role><synaptic circuit><synaptic circuitry><transmission process><ventilation><vocalization><voice box>