Chemoreception and neuroplasticity in respiratory circuits

Area of Science:

• Neuroscience
• Respiratory Physiology
• Computational Biology

Background:

• The respiratory central pattern generator maintains blood gas homeostasis by responding to chemosensory cues.
• Chronic intermittent hypoxia (CIH) induces neuroplasticity, altering respiratory and autonomic outputs, leading to chemoreflex sensitization, active expiration, and hypertension.

Purpose of the Study:

• To test the hypothesis that CIH-induced neuroplasticity involves increased excitability of pre-inspiratory neurons in the pre-Bötzinger complex.
• To elucidate the neural mechanisms underlying active expiration and sympathetic overactivity following CIH exposure.

Main Methods:

• Extended a computational model of the brainstem respiratory-sympathetic network to simulate peripheral and central chemoreflexes post-CIH.
• Incorporated neuronal connections between the nucleus of the solitary tract (NTS), respiratory pattern generator, and sympathetic neurons.
• Simulated neuronal responses to peripheral chemoreflex stimulation.

Main Results:

• Identified potential neuronal groups involved in inspiratory, expiratory, and sympathetic reflex responses during peripheral chemoreflex stimulation.
• Predicted plasticity of channel expression in pre-Bötzinger complex pre-inspiratory neurons due to excessive excitation.
• Showed that increased excitability of pre-inspiratory neurons can lead to active expiration via interactions with retrotrapezoid nucleus expiratory neurons.

Conclusions:

• Neuronal type-specific neuroplasticity in the pre-Bötzinger complex, driven by hypoxia-induced chemoreceptor activation, may underlie sympathetic overactivity and hypertension.
• Computational modeling provides insights into the neural mechanisms of CIH-induced respiratory and autonomic changes.