Neonatal stress augments the hypoxic chemoreflex of adult male rats by increasing AMPA receptor‐mediated modulation
Bibliographic record
Abstract
New Findings What is the central question of this study? Early life exposure to stress augments the hypoxic chemoreflex of adult male rats. This effect predisposes to respiratory instability during sleep. We used pharmacological and neuroanatomical approaches to determine whether a change in glutamatergic neurotransmission contributes to this abnormal respiratory phenotype. What is the main finding and its importance? We initially showed that neonatal stress augments sensitivity to an AMPA/kainate receptor antagonist. Results from autoradiography experiments support this observation because they demonstrate that neonatal stress increases expression of AMPA receptors in key regions that regulate breathing. Region‐specific changes in brain‐derived neurotrophic factor expression may contribute to these changes in glutamatergic neurotransmission. These results bring new insight into the pathophysiology of sleep‐disordered breathing. Neonatal stress disrupts the developmental trajectory of homeostatic systems. Adult (8‐ to 10‐week‐old) male rats exposed to maternal separation (a form of neonatal stress) display several traits reported in patients suffering from sleep‐disordered breathing, including an augmented hypoxic chemoreflex. To understand the mechanisms behind this effect, we tested the hypothesis that neonatal stress augments glutamatergic neurotransmission in three regions involved in respiratory regulation, namely the nucleus of the solitary tract, the paraventricular nucleus of the hypothalamus and the phrenic motor nucleus. Maternal separation was performed for 3 h day −1 from postnatal day 3 to 12. Control pups were undisturbed. Adult rats were instrumented for intracerebroventricular injection of the AMPA/kainate receptor antagonist CNQX (0–4.3 μ m ). Using plethysmography, ventilatory activity was measured at rest in awake animals during normoxia (fractional inspired O 2 = 0.21) and during acute hypoxia (fractional inspired O 2 = 0.12; 20 min). Following vehicle injection, the hypoxic ventilatory response of stressed rats was 35% greater than that of controls. Microinjection of CNQX attenuated the hypoxic ventilatory response, but the effect observed in stressed rats was greater than that in control animals. Autoradiography experiments showed that neonatal stress augments expression of AMPA receptors within the paraventricular nucleus of the hypothalamus and the phrenic motor nucleus. Quantification of brain‐derived neurotrophic factor showed that neonatal stress augments brain‐derived neurotrophic factor expression only within the paraventricular nucleus. We conclude that neonatal stress augments the hypoxic chemoreflex by increasing the efficacy of glutamatergic synaptic inputs projecting onto key respiratory structures, especially the paraventricular nucleus of the hypothalamus. These data provide new insight into the aetiology of sleep‐disordered breathing.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| 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 teacher head, 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".