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Record W3159628964 · doi:10.1016/j.celrep.2021.109036

4E-BP2-dependent translation in cerebellar Purkinje cells controls spatial memory but not autism-like behaviors

2021· article· en· W3159628964 on OpenAlexafffund
Mehdi Hooshmandi, Vinh Tai Truong, Eviatar Fields, Riya Elizabeth Thomas, Calvin Wong, Vijendra Sharma, Ilse Gantois, Patricia Roque, Kleanthi Chalkiadaki, Neil Wu, Anindyo Chakraborty, Soroush Tahmasebi, Masha Prager‐Khoutorsky, Nahum Sonenberg, Aparna Suvrathan, Alanna J. Watt, Christos G. Gkogkas, Arkady Khoutorsky

Bibliographic record

VenueCell Reports · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA regulation and disease
Canadian institutionsMcGill University Health CentreMcGill University
FundersFonds de Recherche du Québec - SantéMcGill University Health CentreCanadian Institutes of Health ResearchSimons Foundation Autism Research InitiativeCanada First Research Excellence FundMcGill University
KeywordsmTORC1CerebellumNeuroscienceTensinTSC1Translation (biology)BiologyPI3K/AKT/mTOR pathwayChemistryCell biologyPTENSignal transductionMessenger RNABiochemistryGene

Abstract

fetched live from OpenAlex

Recent studies have demonstrated that selective activation of mammalian target of rapamycin complex 1 (mTORC1) in the cerebellum by deletion of the mTORC1 upstream repressors TSC1 or phosphatase and tensin homolog (PTEN) in Purkinje cells (PCs) causes autism-like features and cognitive deficits. However, the molecular mechanisms by which overactivated mTORC1 in the cerebellum engenders these behaviors remain unknown. The eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2) is a central translational repressor downstream of mTORC1. Here, we show that mice with selective ablation of 4E-BP2 in PCs display a reduced number of PCs, increased regularity of PC action potential firing, and deficits in motor learning. Surprisingly, although spatial memory is impaired in these mice, they exhibit normal social interaction and show no deficits in repetitive behavior. Our data suggest that, downstream of mTORC1/4E-BP2, there are distinct cerebellar mechanisms independently controlling social behavior and memory formation.

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)0.000
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 score0.022
Threshold uncertainty score0.793

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.009
GPT teacher head0.230
Teacher spread0.221 · 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

Citations15
Published2021
Admission routes2
Has abstractyes

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