Comparison of GABA, Somatostatin, and Corticotrophin-Releasing Hormone Expression in Axon Terminals That Target the Parabrachial Nucleus

Abstract

Abstract Several forebrain areas have been shown to project to the parabrachial nucleus (PBN) and exert inhibitory and excitatory influences on taste processing. Some sources of descending input such as the central nucleus of the amygdala (CeA) might utilize somatostatin (Sst) and/or corticotrophin-releasing hormone (Crh) to influence taste processing in the PBN (Panguluri S, Saggu S, Lundy R. 2009. Comparison of somatostatin and corticotrophin-releasing hormone immunoreactivity in forebrain neurons projecting to taste-responsive and non-responsive regions of the parabrachial nucleus in rat. Brain Res 1298:57–69; Magableh A, Lundy R. 2014. Somatostatin and corticotrophin releasing hormone cell types are a major source of descending input from the forebrain to the parabrachial nucleus in mice. Chem Senses 39:673–682). Since the predominate effect of CeA stimulation on PBN taste-evoked responses is inhibition, this study used transgenic reporter lines (Sst/TdTomato and Crh/TdTomato) and electron microscopy to assess Sst/gamma aminobutyric acid (GABA) and Crh/GABA coexpression in axon terminals within the PBN. Robust expression of Sst and Crh axon terminals was observed in the PBN. The majority of Sst-positive axon terminals were positive for GABA expression, while the majority of Crh terminals were not. The results indicate that Sst-expressing neurons, but not Crh neurons, are a source of GABAergic input to the PBN. To assess whether the CeA is a source of GABAergic input to the PBN, the CeA of Sst-cre mice was injected with cre-dependent enhanced yellow fluorescent protein (EYFP) virus and PBN tissue processed for GABA and EYFP expression. Again, the majority of EYFP Sst-positive axon terminals in the PBN coexpressed GABA. Together, the present results suggest that CeA neurons marked by Sst expression represent a major extrinsic source of GABAergic input to the PBN and this could underlie the predominate inhibitory effect of CeA stimulation on taste-evoked responses in the PBN.