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Record W2306974599 · doi:10.1093/cercor/bhw075

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures

2016· article· en· W2306974599 on OpenAlexfundno aff
Christopher E. Heise, Elham Taha, Luca Murru, Luisa Ponzoni, Angela Cattaneo, Fabrizia Claudia Guarnieri, Caterina Montani, Adele Mossa, Elena Vezzoli, Giulio Ippolito, Jonathan Zapata, Iliana Barrera, Alexey G. Ryazanov, James M. Cook, Michael M. Poe, Michael Rajesh Stephen, Maksym V. Kopanitsa, Roberta Benfante, Francesco Rusconi, Daniela Braida, Maura Francolini, Christopher G. Proud, Flavia Valtorta, Maria Passafaro, Mariaelvina Sala, Angela Bachi, Chiara Verpelli, Kobi Rosenblum, Carlo Sala

Bibliographic record

VenueCerebral Cortex · 2016
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilIstituto Italiano di TecnologiaIsrael Science FoundationMinistry of Health, British ColumbiaMinistry of Science and TechnologyWellcome TrustNational Institute of Mental HealthWellcomeFondazione CariploIsrael Society for NeuroscienceERA-Net NEURON
KeywordsNeuroscienceEpilepsyGABAergicNeurotransmissionInhibitory postsynaptic potentialBiologyExcitatory postsynaptic potentialReceptorGenetics

Abstract

fetched live from OpenAlex

Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy.

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 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 score0.187
Threshold uncertainty score0.505

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.308
Teacher spread0.272 · 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 teacher head, 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

Citations69
Published2016
Admission routes1
Has abstractyes

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