Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Cereb Cortex. 2023 Jun 20;33(13):8232-8246. doi: 10.1093/cercor/bhad110.
Stress-related disorders such as depression and anxiety exhibit sex differences in prevalence and negatively impact both mental and physical health. Affective illness is also frequently accompanied by changes in ventromedial prefrontal cortical (vmPFC) function. However, the neurobiology that underlies sex-specific cortical processing of affective stimuli is poorly understood. Although rodent studies have investigated the prefrontal impact of chronic stress, postmortem studies have focused largely on males and yielded mixed results. Therefore, genetically defined population recordings in behaving animals of both sexes were used to test the hypothesis that chronic variable stress (CVS) impairs the neural processing of affective stimuli in the rodent infralimbic region. Here, we targeted expression of a calcium indicator, GCaMP6s, to infralimbic pyramidal cells. In males, CVS reduced infralimbic responses to social interaction and restraint stress but increased responses to novel objects and food reward. In contrast, females did not have CVS-induced changes in infralimbic activity, which was partially dependent on the ovarian status. These results indicate that both male and female vmPFC cells encode social, stress, and reward stimuli. However, chronic stress effects are sex-dependent and behavior-specific. Ultimately, these findings extend the understanding of chronic stress-induced prefrontal dysfunction and indicate that sex is a critical factor for cortical processing of affective stimuli.
应激相关障碍，如抑郁和焦虑，在患病率上存在性别差异，对心理健康和身体健康都有负面影响。情感疾病也常伴随着腹内侧前额皮质（vmPFC）功能的变化。然而，支持性别特异性皮质对情感刺激进行处理的神经生物学机制仍知之甚少。尽管啮齿动物研究已经调查了慢性应激对前额叶的影响，但尸检研究主要集中在男性身上，结果喜忧参半。因此，本研究使用行为动物的遗传定义群体记录来测试慢性可变应激（CVS）是否会损害啮齿动物下边缘区域对情感刺激的神经处理的假设。在这里，我们将钙指示剂 GCaMP6s 靶向表达于下边缘区的锥体神经元。结果发现，在雄性中，CVS 减少了对社交互动和束缚应激的下边缘区反应，但增加了对新奇物体和食物奖励的反应。相比之下，雌性的下边缘区活动没有 CVS 诱导的变化，而这种变化部分依赖于卵巢状态。这些结果表明，雄性和雌性 vmPFC 细胞都对社会、应激和奖励刺激进行编码。然而，慢性应激的影响具有性别依赖性和行为特异性。最终，这些发现扩展了对慢性应激诱导的前额叶功能障碍的理解，并表明性别是皮质对情感刺激进行处理的一个关键因素。
