Abstract TP105: Increaed GABA <sub>A</sub> Mediated Synaptic Activity and Structural Remodeling in Peri-infarct Cortex Layer 5 in the Post-stroke Rodent Brain.
Bibliographic record
Abstract
Introduction: The mechanisms of functional recovery after stroke are thought to be based on structural and functional changes in brain circuits adjacent to or connected with the stroke site. Deciphering these changes at the synaptic level is key to understanding the re-organization of the synaptic circuitry. Here we use a combined approach of i) array tomography to determine the composition of GABA synapses in the post-stroke mouse brain, with ii) electrophysiology to determine whether stroke leads to functional changes in GABA A receptor-mediated neurotransmission. Methods: A cortical lesion was induced in 12-week-old C57BL/6J male mice using the distal middle cerebral artery occlusion model of ischemia. For array tomography, small tissue was removed from the peri-infarct cortex and ribbons of serial ultrathin sections were obtained. Ribbons were stained with antibodies for synaptic markers. Analysis of the resultant staining pattern was used to quantify GABAergic synapses. In addition, whole-cell patch clamp recordings from acute neocortical brain slices were performed to evaluate GABA-mediated synaptic signaling in the peri-infarct cortex. Behavior was evaluated weekly. Results: At 1 week post-stroke, the array tomography data revealed an increase in the density and proportion of alpha1 subunit-containing GABAergic synapses in layer 5 of the peri-infarct cortex (Density: 0.064 vs 0.036 synapses/μm3. Proportion: 15.3 vs 9.1 %, p<0.05, n=6); no changes were observed in layer2/3. Changes in GABA synapses were transient and returned to basal levels by 1 month. Electrophysiological recordings at 1 week post-stroke showed that GABA A receptor-mediated currents were enhanced in layer 5, but not in layer 2/3. These changes were specific to the pyramidal neurons. Behavioral impairment after stroke was observed only at 1 week compared to sham mice (p<0.05, n=10). Conclusion: Our results suggest that stroke leads to an increased expression of functional GABA A receptors in peri-infarct neocortex and that these changes are layer- and cell type-specific. These synaptic changes may represent a mechanism of post-stroke functional recovery and remapping of surviving circuits.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".