Are chemoreceptive properties of retrotrapezoid nucleus neurons altered following long-term respiratory stress?
(2019) Kioloa colloquium — Location: Kioloa, Australia
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- Abstract
- Phox2b-expressing retrotrapezoid nucleus (RTN) neurons are CO2-responsive and critical in mediating the central respiratory chemoreflex. RTN neurons project to the ventral respiratory column (VRC) which generates the rhythmic breathing pattern. 50% of RTN neurons express the inducible inhibitory neuropeptide transmitter, galanin, which increases by 70% after long term hypercapnia (LH). Here we wished to determine alterations in RTN responsiveness to hypercapnic chemoreflex after LH and characterise the RTN-VRC galaninergic circuitry. Mice (n=5/group) were exposed to LH (8% CO2, balance room air (RA)) or RA, for 10 days. Then, all mice were exposed to acute hypercapnic chemoreflex challenge (AC: 1 hr of 10% CO2 exposure, 40% O2, 50% N2). To determine overall RTN responsiveness, c-Fos and Phox-2b immunohistochemistry (IHC) was conducted. In RA animals, 31 % of RTN neurons were activated following AC, compared to 8% of RTN neurons that were activated under baseline conditions (RA, 10 days, no AC) (p<0.05). In mice that had LH, 26% of RTN neurons were activated following AC, which was not statistically significant to 19% of RTN neurons that were activated under baseline conditions (LH, no AC). Furthermore, RTN neurons were 9% more responsive at night (active state) compared to day (sleep state) (p<0.001). To determine, the responsiveness of the galaninergic RTN neurons, in situ hybridization was conducted for ppGal followed by IHC for c-Fos, currently we are in the process of analysing this data. Finally, the distribution of galanin receptor 1 (GalR1) mRNA was determined in the adult mouse VRC using fluorescent ISH (RNAscope). There was an average of 219 (±13) GalR1+ neurons in the VRC for each animal, of which ~23% were inhibitory (glycinergic) (n=5). After compartmentalization of the VRC, the number of GalR1 neurons in the Botzinger complex was determined to be two-folds higher than in the preBötzinger complex. Furthermore, 10% of GalR1 neurons in the preBötC and 30 % in the BötC were glycinergic. In conclusion, RTN neuronal activation is blunted following LH. The GalR1 (Gi coupled) colocalisation with glycinergic VRC neurons suggests a disinhibition of the VRC neurons especially in the BotC.
- Affiliations
University of New South Wales
Citations
Dereli, A., Yaseen, Z., & Kumar, N. N. (2019). Are chemoreceptive properties of retrotrapezoid nucleus neurons altered following long-term respiratory stress? Kioloa colloquium, Kioloa, Australia.