Somatostatin 2A receptors are not expressed on functionally identified respiratory neurons in the ventral respiratory column

Exogenous somatostatin (SST) has profound inhibitory effects on the ventrolateral medullary (VLM) networks responsible for respiratory rhythm generation. Somatostatin 2a receptors (sst2a) are expressed in the pre-Bӧtzinger Complex, and have therefore been proposed as a feasible neurochemical marker of respiratory neurons. However, no data regarding to overall pattern of sst2a expression in the VLM are available. Here we comprehensively describe the
distribution of sst2a with respect to classical markers of respiratory (glycine transporter 2 mRNA, neurokinin 1 receptor (NK1R)) or cardiovascular (Phox2b, tyrosine hydroxylase (TH)) function in respiratory subnuclei of the ventrolateral medulla and on functionally identified respiratory neurons. Extracellular recordings were made from respiratory-locked neurons in the Bötzinger Complex, pre-Bötzinger Complex, and rostral ventral respiratory group in urethane-anaesthetised, vagotomised and artificially ventilated rats. After functional classification neurons were juxtacellularly labelled with fluorescent dextran or neurobiotin; recovered neurons were processed for sst2a immunoreactivity. Overall, sst2a-immunoreactive neurons were found in a column that started at the ventral aspect of the facial nucleus and extended caudally for several millimetres. sst2a expression strongly co-localized with TH and Phox2b in the rostral VLM C1 region. However, sst2a immunoreactivity was virtually absent in the Bӧtzinger Complex, with no co-localisation of sst2a on glycinergic neurons. In the pre-Bӧtzinger Complex we saw NK1R colocalisation in 54±5% of sst2a-positive neurons (n = 4 rats), but many NK1R positive neurons were also sst2a-negative. 52 functionally identified respiratory interneurons were recovered, including 11 pre-inspiratory pre-Bӧtzinger Complex neurons. Regardless of discharge pattern, none were sst2a-immunoreactive. Our evidence suggests that sst2a is not strongly associated with classical markers of respiratory function in the VLM or in neurons with a phasic discharge pattern. We conclude that sst2a expression is a poor marker of respiratory function in this region.