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Record W4221055354 · doi:10.1002/glia.24150

K <sup>+</sup> efflux through postsynaptic <scp>NMDA</scp> receptors suppresses local astrocytic glutamate uptake

2022· article· en· W4221055354 on OpenAlexfundno aff
Olga Tyurikova, Pei‐Yu Shih, Yulia Dembitskaya, Leonid P. Savtchenko, Thomas J. McHugh, Dmitri A. Rusakov, Alexey Semyanov

Bibliographic record

VenueGlia · 2022
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsnot available
FundersMedical Research CouncilRussian Foundation for Basic ResearchNational Centre for the Replacement, Refinement and Reduction of Animals in ResearchMedical Research Council CanadaNational Natural Science Foundation of ChinaWellcome Trust
KeywordsPostsynaptic potentialBiologyNMDA receptorGlutamate receptorPostsynaptic densityEffluxNeuroscienceReceptorAstrocyteBiophysicsBiochemistryCentral nervous system

Abstract

fetched live from OpenAlex

Abstract Glutamatergic transmission prompts K + efflux through postsynaptic NMDA receptors. The ensuing hotspot of extracellular K + elevation depolarizes presynaptic terminal, boosting glutamate release, but whether this also affects glutamate uptake in local astroglia has remained an intriguing question. Here, we find that the pharmacological blockade, or conditional knockout, of postsynaptic NMDA receptors suppresses use‐dependent increase in the amplitude and duration of the astrocytic glutamate transporter current (I GluT ), whereas blocking astrocytic K + channels prevents the duration increase only. Glutamate spot‐uncaging reveals that astrocyte depolarization, rather than extracellular K + rises per se, is required to reduce the amplitude and duration of I GluT . Biophysical simulations confirm that local transient elevations of extracellular K + can inhibit local glutamate uptake in fine astrocytic processes. Optical glutamate sensor imaging and a two‐pathway test relate postsynaptic K + efflux to enhanced extrasynaptic glutamate signaling. Thus, repetitive glutamatergic transmission triggers a feedback loop in which postsynaptic K + efflux can transiently facilitate presynaptic release while reducing local glutamate uptake.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Science and technology studies, Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.139
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0020.001
Scholarly communication0.0000.001
Open science0.0020.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.037
GPT teacher head0.302
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations22
Published2022
Admission routes1
Has abstractyes

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