Role of p75 neurotrophin receptor in cortical parvalbumin-positive GABAergic interneurons and cognitive flexibility
Why this work is in the frame
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Bibliographic record
Abstract
Parvalbumin (PV)-GABAergic interneurons constitute the majority of interneurons in the cortex and play a key role in the function and synchronization of cortical networks. Alterations in PV-interneuron connectivity, in the medial prefrontal cortex (mPFC), have been related to psychiatric disorders. We have previously shown that the expression of the p75 neurotrophin receptor (p75NTR) regulates the time course of PV cell synapse maturation in a cell-autonomous fashion. Here, we study how p75NTR removal in postnatal PV cells affects the connectivity of PV interneurons and mPFC function in adult PV_Cre;p75NTRlox/lox mice. One important indication of PV cell maturation is the appearance of specialized extracellular matrix structures called perineural nets (PNNs) around the soma and primary dendrites of mature cortical PV cells. Conditional postnatal deletion of p75NTR in PV cells resulted in an increased perineural net (PNN) density and intensity around these cells, along with higher excitatory afferent and inhibitory efferent connectivity in PFC. These mice also showed deficits in attentional set-shifting task, a measure of attention and cognitive flexibility in mPFC, and in extinction of fear memories, both of which rely on mPFC function. Finally, we investigate whether the overexpression of P75NTR in mPFC of adult cKO can rescue PV cell structural deficit. Using a Cre-dependent adeno-associated virus, we observed a significant decrease in PV cell inhibitory efferent connectivity. Analysis on the PNN density and intensity around PV cell somata is currently ongoing. These findings uncover P75NTR as a critical regulator of PV circuit refinement and plasticity in adult PFC by simultaneously controlling PV cellular connectivity underlying cognitive function.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.006 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 it