Early Changes in Striatal Activity and Motor Kinematics in a Huntington's Disease Mouse Model
Bibliographic record
Abstract
BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder with no disease-modifying treatments. Patients experience motor, cognitive, and psychiatric disturbances, and the dorsal striatum is the main target of neurodegeneration. Mouse models of Huntington's disease show altered striatal synaptic signaling in vitro, but how these changes relate to behavioral deficits in vivo is unclear. OBJECTIVES: We aimed to investigate how striatal activity correlates with behavior in vivo during motor learning and spontaneous behavior in a Huntington's disease mouse model at two disease stages. METHODS: We used fiber photometry to record jGCaMP7f fluorescence, a read-out of neuronal activity, in the dorsal striatum of YAC128 (yeast artificial chromosome-128CAG) mice during accelerating rotarod and open-field behavior. RESULTS: Mice showed increased striatal activity on the rotarod, which diminished by late stages of learning, leading to an inverse correlation between latency to fall and striatal activity. The 2- to 3-month-old YAC128 mice did not show a deficit in latency to fall, but displayed significant differences in paw kinematics, including increased paw slip frequency and variability in paw height. These mice exhibited a weaker correlation between latency to fall and striatal activity and aberrant striatal activity during paw slips. At 6 to 7 months, the YAC128 mice showed significantly reduced latency to fall, impaired paw kinematics, and increased striatal activity while on the rotarod. In the open field, the YAC128 mice showed elevated neuronal activity at rest. CONCLUSIONS: We uncovered impaired motor coordination at a stage thought to be premotor manifest in YAC128 mice and aberrant striatal activity during the accelerating rotarod and open-field exploration. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".