Supporting data for Fig 5.

A single exposure to a stressful event can result in enduring changes in behaviour. Long-term modifications in neuronal networks induced by stress are well explored but the initial steps leading to these alterations remain incompletely understood. In this study, we found that acute stress exposure triggers an immediate increase in the firing activity of calretinin-positive neurons in the paraventricular thalamic nucleus (PVT/CR+) that persists for several days in mice. This increase in activity had a causal role in stress-induced changes in spontaneous behaviour. Attenuating PVT/CR+ neuronal activity for only 1 h after the stress event rescued both the protracted increase in PVT/CR+ firing rate and the stress-induced behavioural alterations. Activation of the key forebrain targets (basolateral amygdala, prelimbic cortex, and nucleus accumbens) that mediate defensive behaviour has also been reduced by this post-stress inhibition. Reduction of PVT/CR+ cell activity 5 days later remained still effective in ameliorating stress-induced changes in spontaneous behaviour. The results demonstrate a critical role of the prolonged, post-stress changes in firing activity of PVT/CR+ neurons in shaping the behavioural changes associated with stress. Our data proposes a therapeutic window for intervention in acute stress-related disorders, offering potential avenues for targeted treatment strategies.单次暴露于应激事件即可引发行为的持久性改变。应激诱导的神经元网络长期重塑已得到充分研究，但介导此类改变的初始步骤仍未完全阐明。本研究发现，急性应激暴露会立即触发小鼠丘脑室旁核钙视网膜蛋白阳性神经元（PVT/CR+）的放电活动升高，且该升高状态可持续数日。这种活动升高在应激诱导的自发行为改变中发挥了因果性作用。仅在应激事件发生后1小时内抑制PVT/CR+神经元活动，即可同时逆转PVT/CR+放电速率的持续性升高以及应激诱导的行为异常。该应激后抑制手段还可减弱介导防御行为的关键前脑靶点——基底外侧杏仁核、前边缘皮层与伏隔核的激活水平。即便在应激事件发生5天后再抑制PVT/CR+细胞活动，仍可有效改善应激诱导的自发行为改变。本研究结果证实，应激后PVT/CR+神经元放电活动的持续性改变，在塑造应激相关行为异常中发挥了关键作用。本研究数据为急性应激相关障碍的干预提供了治疗窗口，也为靶向治疗策略提供了潜在方向。