Ventral Hippocampal Afferents to Nucleus Accumbens Encode Both Latent Vulnerability and Stress-Induced Susceptibility
Bibliographic record
Abstract
BACKGROUND: Stress is a major risk factor for depression, but not everyone responds to stress in the same way. Identifying why certain individuals are more susceptible is essential for targeted treatment and prevention. In rodents, nucleus accumbens (NAc) afferents from the ventral hippocampus (vHIP) are implicated in stress-induced susceptibility, but little is known about how this pathway might encode future vulnerability or specific behavioral phenotypes. METHODS: We used fiber photometry to record in vivo activity in vHIP-NAc afferents during tests of depressive- and anxiety-like behavior in male and female mice, both before and after a sex-specific chronic variable stress protocol, to probe relationships between prestress neural activity and behavior and potential predictors of poststress behavioral adaptation. Furthermore, we examined chronic variable stress-induced alterations in vHIP-NAc activity in vivo and used ex vivo slice electrophysiology to identify the mechanism of this change. RESULTS: We identified behavioral specificity of the vHIP-NAc pathway to anxiety-like and social interaction behavior. We also showed that this activity is broadly predictive of stress-induced susceptibility in both sexes, while prestress behavior is predictive only of anxiety-like behavior. We observed a stress-induced increase in in vivo vHIP-NAc activity coincident with an increase in spontaneous excitatory postsynaptic current frequency. CONCLUSIONS: We implicate vHIP-NAc in social interaction and anxiety-like behavior and identify markers of vulnerability in this neural signal, with elevated prestress vHIP-NAc activity predicting increased susceptibility across behavioral domains. Our findings indicate that individual differences in neural activity and behavior play a role in predetermining susceptibility to later stress, providing insight into mechanisms of vulnerability.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".