Prokineticin 2 modulates the excitability of area postrema neurons in vitro in the rat
Bibliographic record
Abstract
Despite recent evidence describing prokineticin 2 (PK2)-producing neurons and receptors in the dorsomedial medulla, little is known regarding the potential mechanisms by which this circadian neuropeptide acts in the medulla to influence autonomic function. Using whole cell electrophysiology, we have investigated a potential role for PK2 in the regulation of excitability in neurons of the area postrema (AP), a medullary structure known to influence autonomic processes in the central nervous system. In current-clamp recordings, focal application of 1 microM PK2 reversibly influenced the excitability of the majority of dissociated AP cells tested, producing depolarizations (38%) and hyperpolarizations (28%) in a concentration-dependent manner. Slow voltage ramps and ion-substitution experiments revealed that a PK2-induced Cl(-) current was responsible for membrane depolarization, whereas hyperpolarizations were the result of inhibition of a nonselective cation current. In contrast to these differential effects on membrane potential, nearly all neurons that displayed spontaneous activity responded to PK2 with a decrease in spike frequency. These observations are in accordance with voltage-clamp experiments showing that PK2 caused a leftward shift in Na(+) channel activation and inactivation gating. Lastly, using post hoc single-cell RT-PCR technology, we have shown that 7 of 10 enkephalin-expressing AP neurons were depolarized by PK2 indicating that PK2 may have specific inhibitory actions on this population of neurons in the AP to reduce their sensitivity to homeostatic signals. These data suggest that the level of AP neuronal excitability may be regulated by PK2, ultimately affecting AP autonomic control.
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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".