Stress-Induced Dysregulation of the Guidance Cue Receptor DCC Alters Corticolimbic Circuit Architecture
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Bibliographic record
Abstract
Elevated expression of the guidance cue receptor gene DCC ( d eleted in c olorectal c ancer ) in the adult prefrontal cortex (PFC) is a hallmark of major depressive disorder. DCC receptors regulate neuronal connectivity and plasticity in adulthood. In male mice, Dcc knockout in the PFC promotes resilience to behavioral dysregulation following chronic social defeat stress (CSDS), whereas Dcc upregulation increases susceptibility. However, the underlying mechanisms remain to be elucidated. We combined CSDS, behavioral tests (i.e. social interaction, nestlet shredding, and dark-light tests), retrograde neuronal tracing, and quantitative neuroanatomical analysis in adult male mice ( N = 90) to investigate if DCC receptors contribute to stress susceptibility/resilience by remodeling dendritic spine architecture of selective PFC neuronal networks. CSDS reduces both mature and newly formed spines on the apical, but not basal, dendrites of PFC pyramidal neurons. This effect is prevented by downregulating DCC receptors in these neurons—a manipulation that also prevents depression-like behaviors, suggesting a mechanistic link. DCC-expressing neurons in the PFC predominantly project to the nucleus accumbens and social defeat stress induces dendritic spine loss specifically in projections from the infralimbic PFC. Notably, knockout of DCC receptors in infralimbic PFC neurons projecting to the nucleus accumbens shell protects against stress-induced social avoidance. DCC receptors may influence susceptibility or resilience to social stress-induced depression-like behaviors by altering the apical dendritic architecture of PFC pyramidal neurons, particularly those projecting to the nucleus accumbens shell. This mechanism may be at play in the neurobiology of depression, pointing at DCC receptors as promising therapeutic targets.
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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 | 0.004 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.007 | 0.001 |
| 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 it