<i>unc5c</i> haploinsufficient phenotype: striking similarities with the <i>dcc</i> haploinsufficiency model
Bibliographic record
Abstract
DCC and UNC5 homologs (UNC5H) are guidance cue receptors highly expressed by mesocorticolimbic dopamine neurons. We have shown that dcc heterozygous mice exhibit increased dopamine, but not norepinephrine, innervation and function in medial prefrontal cortex. Concomitantly, dcc heterozygotes show blunted mesolimbic dopamine release and behavioral responses to stimulant drugs. These changes appear only in adulthood. Recently, we found an adolescent emergence of UNC5H expression by dopamine neurons and co-expression of DCC and UNC5H by single dopamine cells. Here, we demonstrate selective expression of unc5 homolog c mRNA by dopamine neurons in adulthood. We show that unc5c haploinsufficiency results in diminished amphetamine-induced locomotion in male and female mice. This phenotype is identical to that produced by dcc haploinsufficiency and is observed after adolescence. Notably, and similar to dcc haploinsufficiency, unc5c haploinsufficiency leads to dramatic increases in tyrosine hydroxylase expression in the medial prefrontal cortex, but not in the nucleus accumbens. In contrast, medial prefrontal cortex dopamine-β-hydroxylase expression is not altered. We confirmed that UNC5C protein is reduced in the ventral tegmental area of unc5c heterozygous mice, but that DCC expression in this region remains unchanged. UNC5C receptors may also play a role in dopamine function and influence sensitivity to behavioral effects of stimulant drugs of abuse, at least upon first exposure. The striking similarities between the dcc and the unc5c haploinsufficient phenotypes raise the possibility that functions mediated by DCC/UNC5C complexes may be at play.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.000 |
| 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".