Region- and activity-dependent regulation of extracellular glutamate in the brain
Bibliographic record
Abstract
The rapid removal of synaptically-released glutamate is essential to maintain fast excitatory chemical neurotransmission and to prevent NMDA receptors mediated synaptic plasticity impairments and cell death. Here, we used the rapid extracellular fluorescent glutamate sensor, iGluSnFR (intensity-based glutamate sensing fluorescent reporter), and high-speed imaging to quantify relative differences in glutamate clearance rates over a wide range of presynaptic activity in situ in the hippocampus, cortex, striatum and cerebellum of male C57/BL6NCrl mice. We found that the hippocampus was significantly more efficient at clearing synaptically-released glutamate. We also found that pharmacological inhibition of GLT-1, the brain’s most abundant glutamate transporter, slowed clearance rates to only ~ 20-25% of the effect induced by non-selective transporter blockade. In all, our data reveal clear regional differences in glutamate dynamics following neural activity and suggest that non-GLT-1 transporters can make a large contribution to the rate of glutamate clearance when GLT-1 is dysfunctional.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".