Pretreatment with Ampakine CX717 Enhances Long‐Term Facilitation (LTF) of Inspiratory Hypoglossal (XII) Bursting, But Only When Initial Burst Output is Low
Bibliographic record
Abstract
Glutamatergic synaptic transmission is a fundamental component of the neural drive to breathe, and AMPA‐mediated synaptic currents contribute to respiratory rhythmogenesis and respiratory motoneuron depolarization during inspiration. Ampakines are positive allosteric modulators of AMPA receptors, and have been shown to potentiate neuroplasticity in models of long‐term potentiation. The aim of this study was to explore the impact of ampakine CX717 on intermittent‐hypoxia (IH) induced respiratory LTF in urethane anesthetized, vagotomized, and mechanically ventilated adult mice. Ampakine was administered at 15 mg/kg (intraperitoneal injection) 10‐min prior to 3, 1‐min bouts of hypoxia (10% O 2 ). Initial control experiments indicated that a single 15 mg/kg ampakine injection had no persistent impact on XII motor output in this preparation. However, pairing ampakine with IH resulted in enhanced LTF. Thus, over a 90‐min period following IH, the amplitude of the XII inspiratory burst was significantly higher in mice pretreated with ampakine (485 ± 96% of baseline) vs. sham‐injected mice (198 ± 32% of baseline; 2 way repeated measure ANOVA, P<0.05). In addition, the absolute value of the initial pre‐IH baseline XII inspiratory burst amplitude (i.e., raw voltage or “arbitrary units”) was robustly correlated (P<0.001) with the magnitude of LTF (%baseline). Thus, the probability of the ampakine injection evoking a greater LTF was much greater when baseline outputs were low. A similar relationship was not detectable in the non‐ampakine treated mice (P=0.852). We conclude that IH‐induced respiratory LTF can be enhanced by pre‐treatment with ampakine, but the drug is not effective when initial respiratory output is high. These data suggest that ampakines have potential to enhance the impact IH as a neurorehabilitation modality for neurologic conditions associated with reduced respiratory motor output. Support or Funding Information 1 R01 NS080180‐01A1 (DDF), State of Florida Brain and Spinal Cord Injury Research Program (DDF), Canadian Institutes for Health Research (JJG), Craig H. Neilsen Foundation 313369 (SMFT)
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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".