The regulation of subfornical organ neurons
While the central nervous system (CNS) plays a critical role in the regulation of homeostasis, most of the CNS is isolated from constituents of the periphery by a blood-brain-barrier (BBB). The subfornical organ (SFO) is a specialised structure known as a sensory circumventricular organ (sensory CVO) which lacks a BBB, expresses a wide variety and density of membrane receptors, and sends projections to numerous nuclei critical in regulation of homeostasis. Thus the SFO is situated to sense and integrate information about the physiological state of the body and transduce this information to homeostatic control centres in the CNS. The manuscripts comprising this thesis are focused on investigation of the regulation of the rat SFO to maintain homeostasis. In the first manuscript, we investigated the effect of overnutrition in the postnatal pre-weaning stage on gene expression in the SFO by RNAseq, and observed significantly altered expression of 12 transcripts. In the second manuscript, we combined the transcriptomics data from the first chapter with expression data from a previously published microarray study to produce a list of ion channels and G-protein-coupled receptors expressed within the SFO. We also investigated voltage-gated K+, Na+, and Ca2+ currents in SFO neurons, and validated the presence of receptors for the peptide hormones substance P, endothelin, and neurotensin via electrophysiology, in an effort to correlate gene expression data with physiology. Due to the markedly high expression of receptors for neurotensin revealed by the transcriptomics data, in the third manuscript we investigated the electrical effects of neurotensin on SFO neurons. Patch clamp electrophysiology experiments revealed that neurotensin increases the electrical excitability of SFO neurons via an increase in nonselective cation conductance and attenuation of delayed-rectifier voltage-gated K+ currents. Together, these manuscripts represent a significant contribution to our knowledge of the regulation of SFO neurons, thereby improving our understanding of the CNS regulation of homeostasis. We expect these data to be of particular interest to researchers focused on the physiology of homeostasis and the treatment of obesity, hypertension, and metabolic syndrome.
Subfornical organ, Neurotensin, G-protein coupled receptor, Early postnatal overnutrition, Homeostasis, Ion channels, Endothelin, Substance P, Voltage-gated cation channels