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MAPPING NEURAL CIRCUITS CRITICAL TO UPPER AIRWAY FUNCTION AND BREATHING‐SWALLOWING COORDINATION
Author(s) -
Shi Huanan,
Ray Russell Scott
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb584
Subject(s) - brainstem , neuroscience , gabaergic , control of respiration , airway , swallowing , biological neural network , medicine , biology , inhibitory postsynaptic potential , anesthesia , respiratory system , dentistry
Upper airway control and the coordination between swallowing and breathing are essential to avoid the introduction of food or liquids into the lungs. The neural networks underlying upper airway control and swallowing coordination is poorly understood. However, perturbations to these networks may play a role in Sudden Infant Death Syndrome, obstructive sleep apnea, and neurodegenerative disorders such as Parkinson's disease where as much as 44% mortality is attributed to aspiration pneumonia. Thus, there is a clear need to better understand the neural mechanisms that underlie upper airway control, swallowing coordination, and cough reflex throughout life. Though GABAergic signaling is critical to modulate breathing, the functional organization of widespread GABAergic neurons throughout the brainstem remains unclear. We hypothesize that the adult GABAergic system is integrated into distinct functional modules within the brainstem respiratory network aligned along early hindbrain rhombomeric origins. To test this hypothesis, we aim to genetically subdivide the adult brainstem GABAergic system based on their embryonic rhombomere of origin for functional and anatomical mapping studies through the use of intersectional genetic techniques and new chemo‐genetic (DREADD) mouse lines combined with whole body barometric plethysmography and metabolic monitoring. Preliminary studies indicate that inhibitory DREADD hM4De‐mediated perturbation of systemwide GABAergic neurons ( Vgat_FLPo positive neurons) results in increased respiratory output and greater breathing instability while excitatory DREADD hM3D‐mediated systemwide perturbation results in increased sighs and decreased metabolic demand. Examination of the respiratory waveform shows mid‐inspiratory pauses indicative of poor glottal control and increased incidences of cough and expiratory reflex movements. Initial results from rhombomere GABAergic mapping studies suggest that GABAergic involvement in adult chemosensory reflexes may be organized along developmental rhombomeres during embryogenesis. Support or Funding Information McNair Medical Institute This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .