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Record W4415827957 · doi:10.1016/j.nlm.2025.108113

Double dissociation between the involvement of Gadd45α and Gadd45β/γ in the perirhinal cortex and hippocampus of male rats for object memory

2025· article· en· W4415827957 on OpenAlexafffund
Krista A. Mitchnick, Samantha D. Creighton, Karanveer Johal, Sanya Anoop, Bettina E. Kalisch, Gilda Stefanelli, Boyer D. Winters

Bibliographic record

VenueNeurobiology of Learning and Memory · 2025
Typearticle
Languageen
FieldNeuroscience
TopicMemory and Neural Mechanisms
Canadian institutionsUniversity of OttawaUniversity of Guelph
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsPerirhinal cortexDentate gyrusHippocampusCognitive neuroscience of visual object recognitionGene knockdownMemory consolidationRecognition memoryDissociation (chemistry)Downregulation and upregulation

Abstract

fetched live from OpenAlex

• Conflicting findings exist surrounding Gadd45α in object recognition memory. • siRNAs permitted regional evaluation of the Gadd45 family during consolidation. • Gadd45α was required in PRh; Gadd45α mRNA increased in PRh following learning. • Gadd45β/γ was required in HPC; Gadd45β mRNA increased in HPC following learning. • Results resolve conflict and demonstrate regional dissociations in Gadd45 necessity. The GADD45 family of proteins (GADD45α, GADD45β, GADD45γ) has been implicated in DNA demethylation and long-term memory formation. Recently, conflicting findings have emerged surrounding the involvement of Gadd45α in various object recognition tasks. These discrepancies could be due to differences in Gadd45α KO mouse models and/or task parameters. Further, the use of brain-wide KO models precludes our understanding of Gadd45α in specific brain regions such as the hippocampus (HPC), which processes the spatial location of objects, or the perirhinal cortex (PRh), which has a larger role in object identity memory. Here, using a single object recognition task reliant on both the PRh and HPC – the object-in-place (OiP) task – we show that siRNA knockdown of Gadd45β or Gadd45γ, but not Gadd45α, within the dorsal HPC (dHPC) impaired long-term, but not short-term, OiP memory. Further, OiP learning induced an upregulation of Gadd45β mRNA in the dentate gyrus subregion of the dHPC. Within the PRh, siRNA knockdown of Gadd45α, but not Gadd45β or Gadd45γ, impaired long-term, but not short-term, OiP memory, with a concomitant increase in learning induced PRh Gadd45α mRNA. These results clarify previous discrepancies in the literature by demonstrating a clear necessity for Gadd45α in the PRh, but not the dHPC, for the consolidation of long-term object memories.

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 score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0040.001

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 head0.044
GPT teacher head0.311
Teacher spread0.267 · 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

Citations0
Published2025
Admission routes2
Has abstractyes

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