Adverse experiences in early life have a long-term impact on the development of brain, which in turn increases the susceptibility to mental illness during adulthood, especially in female subjects. However, whether and how the visual cortex is affected by these adverse experiences as well as the mechanisms underlying the sex difference are largely unknown. Here, we established a new mouse model of early-life chronic mild stress (ECMS) without anxiety or depression-like behavior in adulthood. ECMS mice showed normal maturation of visual acuity and orientation/direction selectivity, whereas their visual cortical neurons preferred lower spatial frequency (SF) and higher temporal frequency (TF) than control mice. Meanwhile the development of ocular dominance (OD) plasticity was delayed. Specifically, compared with control mice, ECMS mice in the early stage of the critical period (CP) showed a reduction in GABA synthesis enzyme expression as well as lower OD plasticity which could be occluded by diazepam. In contrast, ECMS mice in the late stage of CP showed stronger OD plasticity, accompanied by higher expression of N-methyl-D-aspartate (NMDA) receptor NR2B subunit. Interestingly, only female ECMS mice at adulthood maintained juvenile-like OD plasticity as well as high NR2B expressions. Artificial increase in estradiol level in ECMS males via estradiol supplementary diminished this sex difference. Lastly, OD plasticity was abolished in adult ECMS females either performed with the bilateral ovariectomy in prepuberty, or directly infused with NR2B antagonist Ro 25–6981 into the visual cortex. Overall, our study demonstrates that early adverse experiences have a lasting effect on visual development of mice in a sex-dependent manner, which is mediated by the estradiol-NR2B pathway.

早期的不良经历会对大脑的发展产生长期影响，反过来又增加了成年后对精神疾病的敏感性，尤其是在女性受试者中。然而，这些不良经历以及性别差异背后的机制是否会影响视觉皮层以及如何影响这种皮层很大程度上是未知的。在这里，我们建立了一个新的早期寿命的慢性轻度应激（ECMS）小鼠模型，该模型在成年期没有焦虑或抑郁样行为。ECMS小鼠表现出正常的视敏度和方向/方向选择性成熟度，而与对照小鼠相比，其视觉皮层神经元更喜欢较低的空间频率（SF）和较高的时间频率（TF）。同时，眼优势（OD）可塑性的发展被延迟。具体而言，与对照小鼠相比，处于关键时期（CP）早期的ECMS小鼠表现出GABA合成酶表达的降低以及OD可塑性的降低，这可能是地西epa所致。相反，处于CP晚期的ECMS小鼠表现出较强的OD可塑性，并伴随着N-甲基-D-天冬氨酸（NMDA）受体NR2B亚基的更高表达。有趣的是，只有成年雌性ECMS小鼠才能保持少年似的OD可塑性以及高NR2B表达。通过补充雌二醇人工增加ECMS男性中的雌二醇水平可减少这种性别差异。最后，在成年前经双侧卵巢切除术或直接将NR2B拮抗剂Ro 25–6981注入视皮层的成年ECMS女性中，OD可塑性被取消。总体，