Quantitative fluorescence lifetime imaging uncovers a novel role for KCC2 chloride transport in dendritic microdomains
Bibliographic record
Abstract
Abstract Intracellular chloride ion ([Cl − ] i ) homeostasis is critical for synaptic neurotransmission yet variations in subcellular domains are poorly understood owing to difficulties in obtaining quantitative, high-resolution measurements of dendritic [Cl − ] i . We combined whole-cell patch clamp electrophysiology with simultaneous fluorescence lifetime imaging (FLIM) of the Cl − dye MQAE to quantitatively map dendritic Cl − levels in normal or pathological conditions. FLIM-based [Cl − ] i estimates were corroborated by Rubi-GABA uncaging to measured E GABA . Low baseline [Cl - ] i in dendrites required Cl − efflux via the K + -Cl − cotransporter KCC2 ( SLC12A5 ). In contrast, pathological NMDA application generated spatially heterogeneous subdomains of high [Cl − ] i that created dendritic blebs, a signature of ischemic stroke. These discrete regions of high [Cl − ] i were caused by reversed KCC2 transport. Therefore monitoring [Cl − ] i microdomains with a new high resolution FLIM-based technique identified novel roles for KCC2-dependent chloride transport to generate dendritic microdomains with implications for disease.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".