Absence of testes at puberty impacts functional development of nigrostriatal but not mesoaccumbal dopamine terminals in a wild-derived mouse
Bibliographic record
Abstract
Abstract The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy on evoked dopamine release in male Mus spicilegus , a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts the dopamine systems in M. spicilegus males, we removed the gonads prepubertally at P25 and then examined evoked dopamine release in the dorsomedial, dorsolateral, and nucleus accumbens core regions of striatal slices at P60-70. To measure dopamine release, we used near-infrared catecholamine nanosensors (nIRCats) to enable study of spatial distribution of dopamine release sites in each striatal region. We found that prepubertal gonadectomy led to a significantly reduced density of dopamine release sites and reduced dopamine release at each site in the dorsolateral nigrostriatal system compared to sham controls. By contrast, mesoaccumbal dopamine release was comparable between sham and gonadectomized groups. Our data suggest that during adolescence the development of the nigrostriatal dopamine system is significantly affected by the rise in gonadal hormones in males, while the mesoaccumbal system shows no detectable sensitivity at this time point. These data are consistent with molecular studies in rodents that suggest nigrostriatal neurons are sensitive to androgens at puberty, and extend our understanding of how gonadal hormones could impact the spatial distribution and release potential of dopamine terminals in the striatum. Significance Statement Here we use a wild-derived species, Mus spicilegus , to study adolescent development. This wild-derived species has value over standard lab mice because it is more likely to exhibit evolved developmental programs relevant to dispersal and other natural behaviors. By using this wild-derived species and metrics of evoked dopamine release with spatial resolution, we can test if the rise in gonadal hormones at puberty plays a role in maturation of dopamine terminal function in the striatum. These findings may help us better understand developmental programs in humans that orchestrate changes in behavior at adolescent milestones in contexts of both health and disease.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".