Control of Breathing
Respiration functions through a complex network of neural controls and feedback mechanisms as the body constantly adjusts its breathing rate and tidal volume to meet respiratory metabolic demands.
Several diseases and conditions disrupt the neurological and muscular signals, compromising the body’s ability to breathe normally. Neurologic and muscular disorders like Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), Pompe disease, and sleep-related breathing disorders (SRBD) are key examples of neuromotor impairment that can lead to respiratory insufficiency.
Control of breathing requires complex interactions between the brain, nerves, muscles and lungs, which should be studied simultaneously to gain a deep understanding of breathing behavior.
CONSCIOUS CONTROL, SPONTANEOUS BREATHING
Whole body plethysmography permits a continuous and non-invasive assessment of breathing patterns in conscious subjects. Measurements of respiratory rate, estimated tidal volume, minute ventilation and events like apneas and deep sighs provide valuable insights into the subject’s breathing drive and behavior.
Normoxic, hypoxic and hypercapnic stimuli can be applied to challenge the subject’s respiratory system, and study its response to varying levels of O2 and CO2. These environmental controls also permit the generation of hypoxia-related disease models such as pulmonary hypertension, sleep apnea, and SIDS.
In addition to breathing pattern information, plethysmography can be extended with high-fidelity EEG/EMG signals and blood oxygen sensors, which yield further insights into a subject’s ventilatory control.
- Using plethysmography to determine erythropoietin’s impact on neural control of ventilation – Seaborn et al. J. Methods Mol Biol. 982: 303, 2013.
- Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats – Montandon et al. Am J Physiol., 295: R922, 2008.
- Effect of progesterone on respiratory response to moderate hypoxia and apnea frequency in developing rats – Bairam et al. Respiratory Physiology & Neurobiology. 185-I3, 2013.
ADVANCED LUNG FUNCTION MEASUREMENTS
The flexiVent uses the forced oscillation technique (FOT) to probe the mechanical properties of the lungs with great detail and reproducibility in anesthetized subjects. Various pathologies and reflexes such as bronchoconstriction can dramatically alter lung mechanics (resistance, compliance, tissue mechanics). By silencing specific nerves and neurons, and performing advanced lung function measurements, scientists can isolate the contribution of various neurogenic components associated with respiratory response such as airway hyperreactivity.
- Vagal innervation is required for pulmonary function phenotype in Htr4 −/− mice – House, J. S. et al. American Journal of Physiology-Lung Cellular and Molecular Physiology, 312(4), pp. L520–L530. 2017.
- Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness – Han, L. et al. Nature Neuroscience. Springer US, 21(3), pp. 324–328. 2018.
- Respiratory disturbances in a mouse model of Parkinson’s disease – Oliveira, L. M. et al. Experimental Physiology, 104(5), pp. 729–739. 2019.
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