Leptin and Amylin Influence the Excitability of Area Postrema Neurons, Possibly via cAMP‐Mediated Mechanisms
Bibliographic record
Abstract
The area postrema (AP), a sensory circumventricular organ with important roles in central autonomic regulation, has been shown to possess amylin and leptin receptors, suggesting a role for the AP in modulating peripheral signals indicating energy status. The present study was undertaken to examine the effects of leptin receptor activation on dissociated AP neurons and to elucidate potential mechanism(s) underlying such effects. Whole cell current clamp recordings demonstrated that leptin (10nM) influenced the excitability of 51% (42/82) of AP neurons. The majority of responsive neurons (62%) exhibited a depolarization (mean Δ MP = 5.3 ± 0.7 mV, n=26) in response to leptin administration, while the remaining affected cells (16/42) hyperpolarized (mean Δ MP = ‐5.96 ± 0.95 mV, n=16). We next examined the responsiveness of single AP neurons to consecutively applied leptin and amylin. Both peptides influenced the same population of AP neurons as 5 of 7 cells that depolarized in response to leptin administration also depolarized in response to amylin (10nM). In order to elucidate the mechanism(s) of leptin and amylin actions in AP, we utilized Fluorescence Resonance Energy Transfer (FRET) to determine the effect of leptin and amylin on cAMP levels in single AP neurons. Both leptin (25nM) and amylin (100nM) elevated cAMP levels in the same dissociated AP neurons to approximately 35% of that induced by a maximal concentration of the adenylate cyclase activator, forskolin (1μM) used in combination with IBMX (100μM). These observations that leptin and amylin influence a subpopulation of AP neurons, possibly mediated by cAMP mechanism, supports a role for the AP as a CNS location at which these circulating signals may act to influence central control of energy balance.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".