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.

中文翻译：

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伏隔核的腹侧海马传入神经编码潜在脆弱性和压力诱导的易感性

背景压力是抑郁症的主要危险因素，但并非每个人都以相同的方式应对压力。确定某些个体更易感的原因对于有针对性的治疗和预防至关重要。在啮齿动物中，来自腹侧海马体 (vHIP) 的伏隔核 (NAc) 传入神经与压力诱导的易感性有关，但对该通路如何编码未来的脆弱性或特定的行为表型知之甚少。方法 我们在性别特异性慢性可变应激方案之前和之后，在雄性和雌性小鼠的抑郁和焦虑样行为测试期间，使用纤维光度法记录 vHIP-NAc 传入神经的体内活动，以探测预应力神经元之间的关系。活动和行为以及压力后行为适应的潜在预测因素。此外，我们检查了体内 vHIP-NAc 活性的慢性可变压力诱导的改变，并使用离体切片电生理学来确定这种变化的机制。结果我们确定了 vHIP-NAc 通路对焦虑样和社交互动行为的行为特异性。我们还表明，这种活动广泛地预测了两性的压力诱发的易感性，而预应力行为仅预测了焦虑样行为。我们观察到压力诱导的体内 vHIP-NAc 活性增加与自发兴奋性突触后电流频率的增加一致。结论 我们将 vHIP-NAc 与社交互动和类似焦虑的行为联系起来，并确定了这种神经信号中的脆弱性标记，具有升高的预应力 vHIP-NAc 活性预测跨行为域的易感性增加。我们的研究结果表明，神经活动和行为的个体差异在预先确定对后期压力的易感性方面发挥着作用，提供了对脆弱性机制的深入了解。