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<sup>+</sup>) 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<sup>+</sup> interneuron dysfunction remain largely unclear. Here, we found that a deficiency of Biorientation Defective 1 (<italic>Bod1</italic>) in PV<sup>+</sup> interneurons led to an ASD-like phenotype in <italic>Pvalb-Cre</italic>;<italic>Bod1</italic><sup><italic>f/f</italic></sup> mice. Mechanistically, we observed that <italic>Bod1</italic> deficiency induced hypoactivity of PV<sup>+</sup> 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, <italic>Bod1</italic> deficiency decreased the power of high-gamma oscillation, assessed by <italic>in vivo</italic> multi-channel electrophysiological recording. Furthermore, we found that <italic>Bod1</italic> deficiency enhanced the inwardly rectifying K<sup>+</sup> current, leading to an increase in the resting membrane potential of PV<sup>+</sup> interneurons. Importantly, the gain-of-function of <italic>Bod1</italic> improved social deficits and stereotypical behaviors in <italic>Pvalb-Cre</italic>;<italic>Bod1</italic><sup><italic>f/f</italic></sup> mice. These findings provide mechanistic insights into the PV<sup>+</sup> interneuron dysfunction and suggest new strategies for developing PV<sup>+</sup> interneuron-targeted therapies for ASD.
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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 | 0.009 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.005 | 0.010 |
| Science and technology studies | 0.001 | 0.005 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.001 | 0.005 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".