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Record W3048258652 · doi:10.1038/s41467-020-17824-y

Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization

2020· article· en· W3048258652 on OpenAlexafffund
Francesco Ferrini, Jimena Pérez-Sánchez, Samuel Ferland, Louis-Étienne Lorenzo, Antoine G. Godin, Isabel Plasencia-Fernández, Martin Cottet, Annie Castonguay, Feng Wang, Chiara Salio, Nicolas Doyon, Adalberto Merighi, Yves De Koninck

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicPain Mechanisms and Treatments
Canadian institutionsUniversité LavalShriners Hospitals for Children - Canada
FundersUniversità degli Studi di TorinoRegione PiemonteConsejo Nacional de Ciencia y TecnologíaCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaEuropean Commission
KeywordsNeuroscienceSpinal cordBiophysicsChemistrySynaptic plasticityNociceptionExcitatory postsynaptic potentialBiologyCell biologyReceptorBiochemistryInhibitory postsynaptic potential

Abstract

fetched live from OpenAlex

Abstract GABAA/glycine-mediated neuronal inhibition critically depends on intracellular chloride (Cl−) concentration which is mainly regulated by the K+-Cl−co-transporter 2 (KCC2) in the adult central nervous system (CNS). KCC2 heterogeneity thus affects information processing across CNS areas. Here, we uncover a gradient in Cl−extrusion capacity across the superficial dorsal horn (SDH) of the spinal cord (laminae I-II: LI-LII), which remains concealed under low Cl−load. Under high Cl−load or heightened synaptic drive, lower Cl−extrusion is unveiled in LI, as expected from the gradient in KCC2 expression found across the SDH. Blocking TrkB receptors increases KCC2 in LI, pointing to differential constitutive TrkB activation across laminae. Higher Cl−lability in LI results in rapidly collapsing inhibition, and a form of activity-dependent synaptic plasticity expressed as a continuous facilitation of excitatory responses. The higher metaplasticity in LI as compared to LII differentially affects sensitization to thermal and mechanical input. Thus, inconspicuous heterogeneity of Cl−extrusion across laminae critically shapes plasticity for selective nociceptive modalities.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.036
GPT teacher head0.295
Teacher spread0.259 · 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations59
Published2020
Admission routes2
Has abstractyes

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