Peptidergic inputs to the ventral respiratory column in rodents and characterisation of the RTN in a piglet model of SIDS

Study 1: Central respiratory chemoreceptors assist in the detection of CO2 and the implementation of ventilatory responses in order to maintain circulatory homeostasis. They contribute heavily to apnea termination, autoresuscitation, and arousal in response to hypoxia and hypercapnia. Activation of central chemoreceptors drives respiratory neurons in the ventral respiratory column (VRC), to enhance their excitability and activity of the respiratory network.
Previous studies have identified galanin mRNA as a specific marker of RTN neurons in the rat (Stornetta et al 2009. Furthermore, RTN galanin innervates VRC neurons and microinjection of galanin into the VRC induces apnoea by inhibiting phrenic nerve activity and ventilatory chemoreflex responses (Abbott et al., 2009a). Our recent (see other 2019 CCCFD abstract) data assigns a role to galanin in the RTN in chemoreflex adaptation to long-term hypercapnia. We also identified a subset of neurons in the ventral respiratory column that express galanin receptors. Here, we identify all galaninergic sources of inputs to the VRC and identify those which are stimulated by acute hypercapnia chemoreflex challenge. This better characterises the known pharmacological effects of galanin agonist/antagonist at the VRC, and determines if galanin receptors in the VRC are substrates solely for galanin innervation arising from the RTN.
Study 2: Dysfunction or immaturity in centrally located brainstem networks controlling upper airway functions may contribute to respiratory issues, by increasing the risk for events such as apneas, or by reducing autonomic responses to airway obstruction during sleep. Furthermore, it has been suggested that prolonged apnea, might be causal in SIDS. Chemoreception is vital to normal respiratory function, and may be impaired in Sudden Infant Death Syndrome (SIDS). This study therefore sought to identify the RTN in a piglet model of SIDS and determine changes in Phox2b-immunoreactivity following exposure to intermittent hypercapnic hypoxia, using immunohistochemistry in formalin-fixed paraffin-embedded tissue. We found that the location and neurochemical signature of the piglet RTN are comparable to the rodent RTN, although were unable to determine changes to Phox2b-expression in the piglet model of SIDS due to tissue availability. However, given the homology of chemoreceptive architecture between mammals and the vital function of the RTN in responding to CO2, further research on the RTN in piglets and human infants may provide insight into a potential relationship between SIDS and impaired chemoreception.