Upregulated inwardly rectifying K<sup>+</sup> current-mediated hypoactivity of parvalbumin interneurons underlies autism-like deficits in <i>Bod1</i>-deficient mice
Bibliographic record
Abstract
Parvalbumin-positive (PV+) interneuron dysfunction is believed to be linked to autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors. However, the mechanisms behind PV+ interneuron dysfunction remain largely unclear. Here, we found that a deficiency of Biorientation Defective 1 (Bod1) in PV+ interneurons led to an ASD-like phenotype in Pvalb-Cre;Bod1f/f mice. Mechanistically, we observed that Bod1 deficiency induced hypoactivity of PV+ interneurons and hyperactivity of calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) neurons in the medial prefrontal cortex, as determined by whole-cell patch-clamp recording. Additionally, Bod1 deficiency decreased the power of high-gamma oscillation, assessed by in vivo multi-channel electrophysiological recording. Furthermore, we found that Bod1 deficiency enhanced the inwardly rectifying K+ current, leading to an increase in the resting membrane potential of PV+ interneurons. Importantly, the gain-of-function of Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre;Bod1f/f mice. These findings provide mechanistic insights into the PV+ interneuron dysfunction and suggest new strategies for developing PV+ interneuron-targeted therapies for ASD.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".