In this series of studies funded by the NIH, we will determine the importance of specific neuromodulators within a brainstem region critical to the ventilatory CO2 chemoreflex. Understanding these fundamental neural mechanisms is critical to complete the understanding of respiratory-related diseases thought to result from altered chemoreception in humans, including sudden infant death syndrome (SIDS).
In healthy animals, raphe-derived neuromodulators like 5-HT, substance P and thyrotropin-releasing hormone (TRH) act to increase the excitability of glutamatergic phox2b-expressing neurons in the retrotrapezoid nucleus (RTN). Based on a series of experiments we've done previously (Puissant et al., 2015), we think that these neuromodulators are deficient in a unique rat strain that essentially lacks a ventilatory CO2 response called Brown Norway (BN) rats. If these neurochemicals made and released from 5-HT producing neurons are important for a robust CO2 chemoreflex, then blocking the post-synaptic receptors within the RTN should blunt the ventilatory response to hypercapnia in normal rats. Similarly, if we stimulate these neuromodulatory receptors in the RTN of BN rats, we might augment their already blunted ventilatory response to high CO2. This is the major question Dr. Clarissa Muere is currently addressing in the lab.