p75 neurotrophin receptor in pre-adolescent prefrontal PV interneurons promotes cognitive flexibility in adult mice
Bibliographic record
Abstract
Abstract Parvalbumin (PV)-positive GABAergic cells provide robust perisomatic inhibition to neighboring pyramidal neurons and regulate brain oscillations. Alterations in PV interneuron connectivity and function in the medial prefrontal cortex (PFC) have been consistently reported in psychiatric disorders associated with cognitive rigidity, suggesting that PV cell deficits could be a core cellular phenotype in these disorders. p75 neurotrophin receptor (p75NTR) regulates the time course of PV cell maturation in a cell-autonomous fashion. Whether p75NTR expression during postnatal development affects adult prefrontal PV cell connectivity and cognitive function is unknown. We generated transgenic mice with conditional knockout (cKO) of p75NTR in postnatal PV cells. We analysed PV cell connectivity and recruitment following a tail pinch, by immunolabeling and confocal imaging, in naïve mice or following p75NTR re-expression in pre- or post-adolescent mice using Cre-dependent viral vectors. Cognitive flexibility was evaluated using behavioral tests. PV cell-specific p75NTR deletion increased both PV cell synapse density and the number of PV cells surrounded by perineuronal nets, a marker of mature PV cells, in adult PFC but not visual cortex. Both phenotypes were rescued by viral-mediated re-introduction of p75NTR in pre-adolescent but not in post-adolescent PFC. Prefrontal cortical PV cells failed to upregulated c-Fos following a tail-pinch stimulation in adult cKO mice. Finally, cKO mice showed impaired fear memory extinction learning as well as deficits in a rule set-shifting task. These findings suggest that p75NTR expression in adolescent PV cells contributes to the finetuning of their connectivity and promotes cognitive flexibility in adulthood.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".