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Record W4388233452 · doi:10.7554/elife.90832.1

Restoration of locomotor function following stimulation of the A13 region in Parkinson’s mouse models

2023· preprint· en· W4388233452 on OpenAlexafffund
Linda Kim, Adam P Lognon, Sandeep Sharma, M. A. Tran, Taylor Chomiak, Stephanie Tam, Claire McPherson, Shane E. A. Eaton, Zelma H. T. Kiss, Patrick J. Whelan

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldMedicine
TopicNeurological disorders and treatments
Canadian institutionsHotchkiss Brain InstituteUniversity of Calgary
FundersParkinson CanadaCanadian Institutes of Health ResearchCumming School of Medicine, University of CalgaryFaculty of Veterinary Medicine, University of CalgaryNatural Sciences and Engineering Research Council of CanadaHotchkiss Brain Institute, University of Calgary
KeywordsStimulationFunction (biology)NeuroscienceParkinson's diseasePhysical medicine and rehabilitationPsychologyMedicineBiologyInternal medicineCell biology

Abstract

fetched live from OpenAlex

Abstract Parkinson’s disease (PD) is characterized by extensive motor and non-motor dysfunction, including gait disturbance, which is difficult to treat effectively. This study explores the therapeutic potential of targeting the A13 region, a dopamine-containing area of the medial zona incerta (mZI) that has shown relative preservation in PD models. The A13 is identified to project to the mesencephalic locomotor region (MLR), with a subpopulation of cells displaying activity correlating to movement speed, suggesting its potential involvement in locomotor function. We show that photoactivation of this region can alleviate bradykinesia and akinetic symptoms in a mouse model of PD, revealing the presence of preserved parallel motor pathways for movement. We identified areas of preservation and plasticity within the mZI connectome using whole-brain imaging. Our findings suggest a global remodeling of afferent and efferent projections of the A13 region, highlighting the zona incerta’s role as a crucial hub for the rapid selection of motor function. Despite endogenous compensatory mechanisms proving insufficient to overcome locomotor deficits in PD, our data demonstrate that photostimulation of the A13 region effectively restores locomotor activity. The study unveils the significant pro-locomotor effects of the A13 region and suggests its promising potential as a therapeutic target for PD-related gait dysfunction.

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 score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.094
GPT teacher head0.298
Teacher spread0.204 · 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
Published2023
Admission routes2
Has abstractyes

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