Serotonergic modulation of <i>Locus coeruleus</i> (LC) neurons in the newborn rat
Bibliographic record
Abstract
Serotonergic (5HT) and noradrenergic (NA) neurons project throughout the CNS where they influence brain development and modulate many processes including breathing. The degree to which these modulatory systems interact is unknown. However, 5HT is released in the LC, a NA nucleus involved in central chemosensitivity. Also, exposure of rats to 5HT reuptake inhibitors (SSRIs) perinatally results in adults with hyperexcitable LC neurons. As a significant number of pregnant women take SSRIs, this study aimed to: (1) investigate the effects of perinatal fluoxetine on the ventilatory responses of newborn rats to 7% CO 2 ; (2) assess in naïve newborn rats the mechanisms by which 5HT affects the excitability of LC neurons. Neonates exposed to fluoxetine (E15‐21) had a hypercapnic tidal volume response 31% greater than control. Of 150 whole‐cell voltage‐clamped LC neurons, 101 responded to 5HT (100µM) with an inward current (‐30±3 pA), 18 responded with oscillations (freq of 0.4±0.1 Hz), and 31 did not respond. 5HT 3 R agonists had no effect. 5HT 2 R agonists (PNU22394 & TCB‐2, 100µM) evoked 3 responses: an 822% increase in the freq of glutamatergic mEPSCs (29/37 neurons); an inward current (‐15±2 pA; 22% increase in R N , 16/37); and a nitrendipine‐sensitive 0.1 Hz oscillation (5/37). The 5‐HT 1A R agonist 8‐OH‐DPAT (50µM) induced an inward current (‐14±3 pA, 6/11), while Sumatriptan, a 5HT 1ABD R agonist had no effect. These data demonstrate that perinatal SSRI exposure alters respiratory chemosensitivity. Part of this effect may reflect diverse actions of 5HT on LC neurons that include a presynaptic 5HT 2 ‐mediated increase in glutamatergic EPSCs, and postsynaptic facilitation of Ca 2+ ‐dependent membrane oscillations and a 5HT 2 /5HT 1A ‐ inward current. Support: CIHR, WCHRI, AIHS, CNPq, FAPESP.
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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".