Chronic α5‐ <scp>GABA</scp> ‐A Receptor Potentiation Promotes Mouse Adult Hippocampal Neurogenesis
Bibliographic record
Abstract
Several lines of evidence implicate adult hippocampal neurogenesis (AHN) in cognitive functions, in mood- and anxiety-related behaviors, and in the therapeutic effects of antidepressants. Augmenting α5-γ-Aminobutyric acid type A (GABAA) receptor function has shown neurotrophic effects in stress and aged models, but its impact on mouse AHN remains unknown. Adult male 129S6/SvEvTac mice (n = 30 total) were treated for 6 weeks with GL-II-73, an α5-GABAA-R-positive allosteric modulator (α5-PAM) [30 mg/kg, per os, (P.O.)] or fluoxetine, a prototypical selective serotonin reuptake inhibitor known to increase AHN (18 mg/kg, P.O.). Proliferation in the subgranular zone of the dentate gyrus (DG) was assessed by the level of Ki67, a marker of dividing cells; survival of the young neurons was assessed by retention of the 5-Bromo-2´-Deoxyuridine (BrdU) nucleotide analog injected 2 weeks before sacrifice. Finally, maturation of young adult-born neurons was evaluated by measuring the fraction of BrdU-positive cells that are also DCX and/or NeuN-positive, capturing overall maturation and speed of maturation. Similarly to fluoxetine, a chronic treatment with GL-II-73 stimulated all stages of AHN, significantly increasing neuronal progenitor proliferation, survival of adult-born granule cells, and maturation of young neurons in the DG of the hippocampus. Chronic treatment with GL-II-73, a α5-GABAA-R-positive allosteric modulator, increased AHN, including cellular proliferation, survival, and maturation of newborn neurons, to levels comparable to fluoxetine.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
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".