Post‐pubertal emergence of a dopamine phenotype in netrin‐1 receptor‐deficient mice
Bibliographic record
Abstract
During the pubertal period the mesocortical dopamine (DA) system undergoes substantial reorganization of neuronal connectivity and functional refinement. Netrins are guidance cues involved in the organization of neuronal circuitry. We have previously shown that adult mice that develop with reduced levels of the netrin-1 receptor [deleted in colorectal cancer (DCC)] display selective reorganization of mesocortical DA circuitry, show enhanced mesocortical DA function and exhibit a behavioural phenotype opposite to that observed in animal models of schizophrenia. Here we assess whether the dcc behavioural and DA phenotypes are present prior to the maturation of the mesocortical DA system by comparing dcc-heterozygous and wild-type mice at the post-weaning and peri-pubertal periods on various indices of DA function. At both the post-weaning and peri-pubertal ages, but unlike in adulthood, dcc-heterozygous and wild-type mice show no differences in the number of midbrain DA neurones or in tyrosine hydroxylase protein levels in the medial prefrontal cortex. Furthermore, the elevated baseline concentration of mesocortical DA and DA metabolites observed in adult dcc-heterozygous mice is not present in either post-weanling or peri-pubertal mice. Interestingly, post-weanling, but not peri-pubertal, dcc-heterozygous mice show greater baseline concentrations of DA metabolites in the nucleus accumbens, opposite to what was observed in adulthood. Finally, neither post-weanling nor peri-pubertal dcc-heterozygous mice demonstrate the blunted amphetamine-induced locomotor response observed in adulthood. Thus, these findings show that the 'protective' dcc phenotype has a post-pubertal emergence and indicate that DCC may play a role in the normal maturation of the mesocorticolimbic DA system.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 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".