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Record W4388233300 · doi:10.7554/elife.90832.1.sa4

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

2023· peer-review· en· W4388233300 on OpenAlexaff
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
Typepeer-review
Languageen
FieldMedicine
TopicNeurological disorders and treatments
Canadian institutionsHotchkiss Brain InstituteUniversity of Calgary
Fundersnot available
KeywordsZona incertaNeuroscienceSubthalamic nucleusIndirect pathway of movementDopaminergicBiologyParkinson's diseaseDeep brain stimulationEfferentDopamineMedicineAfferentCentral nervous systemStriatumDiseaseInternal medicine

Abstract

fetched live from OpenAlex

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.This work examines the function of the A13 nucleus in locomotion, an area with direct connectivity to locomotor regions in the brainstem. Our work shows that A13 stimulation can restore locomotor function and improve bradykinesia symptoms in a PD mouse model.

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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Commentary · Consensus signal: none
Teacher disagreement score0.230
Threshold uncertainty score0.770

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0050.003
Insufficient payload (model declined to judge)0.2300.079

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 head0.115
GPT teacher head0.351
Teacher spread0.236 · 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 designNot applicable
Domainnot available
GenreCommentary

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 routes1
Has abstractyes

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