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Record W4406211659 · doi:10.1101/2025.01.09.632139

Altered developmental profile of the cortical head-direction signal in a rat model of Fragile X Syndrome

2025· preprint· en· W4406211659 on OpenAlexaff
Adrian J. Duszkiewicz, Antonis Asiminas, Paul A. Dudchenko, Adrien Peyrache, Emma R. Wood

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
Fundersnot available
KeywordsHead (geology)Fragile X syndromeSIGNAL (programming language)PsychologyAudiologyNeuroscienceMedicineBiologyComputer sciencePsychiatryPaleontology

Abstract

fetched live from OpenAlex

Abstract Fragile X Syndrome (FXS) is a common inherited monogenic cause of autism spectrum disorder and intellectual disability (ASD/ID), but the neural mechanisms underlying its symptoms remain unclear. Here, we investigate the development of the head-direction (HD) system in a rat model of FXS ( Fmr1 −/y rats) and its role in spatial cognition. Using high-density silicon probes, we recorded neuronal activity in the postsubiculum (PoSub), a cortical hub of the HD system, during exploration and sleep in juvenile and adult Fmr1 −/y and wild-type (WT) rats. Surprisingly, juvenile Fmr1 −/y rats exhibited enhanced HD tuning characterized by sharper directional tuning curves and improved stability of the HD signal in relation to the external environment. This enhancement was intrinsic to the HD circuit and persisted across behavioral and sleep states. However, by adulthood, HD tuning in Fmr1 −/y rats became unstable, with increased drift in the allocentric reference frame despite intact intrinsic HD dynamics. These findings reveal a transient enhancement of spatial coding in the HD system of juvenile Fmr1 −/y rats, followed by a degradation in adulthood, mirroring the developmental regression often observed in autism. Overall, our work reveals network-level dysfunctions in FXS and their developmental trajectories.

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 score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.013
GPT teacher head0.218
Teacher spread0.205 · 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 routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenetics and Neurodevelopmental Disorders→French-language works237,207→