The regulation of subfornical organ neurons
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".