Differential galanin expression by chemoreceptor neurons in mouse following long term hypercapnia challenge
Dept Pharmacology, UNSW Sydney.
The primary role of breathing in mammals is to maintain blood gases within a narrow range. Glutamatergic chemoreceptor neurons in the retrotrapezoid nucleus (RTN) are critical in mediating the central respiratory chemoreflex, the primary homeostatic mechanism used by mammals to control blood carbon dioxide (CO2) levels. RTN neurons extensively project to the ventral respiratory column (VRC), which is located in the ventrolateral medulla (VLM) and generates the rhythmic breathing pattern. Interestingly, RTN neurons also express the inducible neuropeptide transmitter galanin and previous studies have demonstrated that injection of galanin into the VRC induces apnoea by inhibiting breathing and ventilatory chemoreflex responses. We hypothesise that long-term exposure to elevated environmental CO2 elicits chronic chemoreceptor stimulation, resulting in altered regulation of galanin neurotransmission in the RTN, which adjusts the central respiratory chemoreflex. Here we demonstrate the distribution of preprogalanin (ppGal) and galanin receptor 1 (GalR1) mRNA in the adult C57Bl6 mouse RTN and VLM respectively, using qualitative PCR and in situ hybridisation. We also measured ppGal mRNA expression in the RTN, VLM, NTS, and cerebellum, during exposure to room air (0% CO2) or hypercapnia (5% CO2, balance room air) for 3, 6 or 8 hours (short term challenge) or continuously for 10 days (long term challenge). Our main qPCR findings were that ppGal mRNA levels increased by 62% in the RTN after long term hypercapnia (10 days) compared to room air (p<0.001). No changes in gene expression were observed in the RTN following short term hypercapnia. Conversely, ppGal expression in the VLM decreased by 32% following short term hypercapnia (p<0.05) however no changes were observed after long term challenge. In summary we have identified a role for peptidergic circuits in plasticity arising in the RTN, during long term adaptation of breathing to respiratory stressors.