Dysfunctional striatal dopamine signaling in Huntington's disease
Bibliographic record
Abstract
Dopamine signaling in the striatum is critical for a variety of behaviors including movement, behavioral flexibility, response to reward and many forms of learning. Alterations to dopamine transmission contribute to pathological features of many neurological diseases, including Huntington's disease (HD). HD is an autosomal dominant genetic disorder caused by a CAG repeat expansion in the Huntingtin gene. The striatum is preferentially degenerated in HD, and this region receives dopaminergic input from the substantia nigra. Studies of HD patients and genetic rodent models have shown changes to levels of dopamine and its receptors in the striatum, and alterations in dopamine receptor signaling and modulation of other neurotransmitters, notably glutamate. Throughout his career, Dr. Michael Levine's research has furthered our understanding of dopamine signaling in the striatum of healthy rodents and HD mouse models. This review will focus on the work of his group and others in elucidating alterations to striatal dopamine signaling that contribute to pathophysiology in HD mouse models, and how these findings relate to human HD studies. We will also discuss current and potential therapeutic interventions for HD that target the dopamine system, and future research directions for this field.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.003 |
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 source (direct Gemma or distilled Codex), 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".