BACKGROUND When exposed to chronic social stress, animals display behavioral changes that are relevant to depressive-like phenotypes. However, the cascading relationship between incremental stress exposure and neural dysfunctions over time remains incompletely understood. METHODS We characterized the longitudinal effect of social defeat on goal-directed actions and prefrontal cortical activity in mice using a novel head-fixed sucrose preference task and two-photon calcium imaging. RESULTS Behaviorally, stress-induced loss of reward sensitivity intensifies over days. Motivational anhedonia, the failure to translate positive reinforcements into future actions, requires multiple sessions of stress exposure to become fully established. For neural activity, individual layer 2/3 pyramidal neurons in the cingulate and medial secondary motor subregions of the medial prefrontal cortex have heterogeneous responses to stress. Changes in ensemble activity differ significantly between susceptible and resilient mice after the first defeat session and continue to diverge following successive stress episodes before reaching persistent abnormal levels. CONCLUSIONS Collectively, these results demonstrate that the cumulative impact of an ethologically relevant stress can be observed at the level of cellular activity of individual prefrontal neurons. The distinct neural responses associated with resilience versus susceptibility suggests the hypothesis that the negative impact of social stress is neutralized in resilient animals, in part through an adaptive reorganization of prefrontal cortical activity.

中文翻译：

---

社会压力对奖励引导行为和前额皮质活动的累积影响

背景当暴露于慢性社会压力时，动物表现出与抑郁样表型相关的行为变化。然而，随着时间的推移，增加的压力暴露与神经功能障碍之间的级联关系仍未完全了解。方法 我们使用一种新的头部固定蔗糖偏好任务和双光子钙成像来描述社交失败对小鼠目标导向行为和前额皮质活动的纵向影响。结果 在行为上，压力引起的奖励敏感性丧失会随着时间的推移而加剧。动机性快感缺乏，未能将积极的强化转化为未来的行动，需要多次压力暴露才能完全建立起来。对于神经活动，内侧前额叶皮层扣带回和内侧次级运动亚区中的单个第 2/3 层锥体神经元对压力有不同的反应。在第一次失败会议后，易感小鼠和有弹性小鼠的整体活动变化显着不同，并且在达到持续异常水平之前连续出现压力事件后继续分化。结论 总的来说，这些结果表明，可以在单个前额叶神经元的细胞活动水平上观察到与行为学相关的压力的累积影响。与复原力和易感性相关的不同神经反应表明社会压力的负面影响在有复原力的动物中被中和的假设，部分是通过前额皮质活动的适应性重组。