The prefrontal cortex, particularly its medial subregions (mPFC), mediates critical functions such as executive control, behavioral inhibition, and memory formation, with relevance for everyday functioning and psychopathology. Despite broad characterization of the mPFC in multiple model organisms, the extent to which mPFC structure and function vary according to an individual's sex is unclear – a knowledge gap that can be attributed to a historical bias for male subjects in neuroscience research. Recent efforts to consider sex as a biological variable in basic science highlight the great need to close this gap. Here we review the knowns and unknowns about how rodents categorized as male or female compare in mPFC neuroanatomy, pharmacology, as well as in aversive, appetitive, and goal- or habit-directed behaviors that recruit the mPFC. We propose that long-standing dogmatic concepts of mPFC structure and function may not remain supported when we move beyond male-only studies, and that empirical challenges to these dogmas are warranted. Additionally, we note some common pitfalls in this work. Most preclinical studies operationalize sex as a binary categorization, and while this approach has furthered the inclusion of non-male rodents it is not as such generalizable to what we know of sex as a multidimensional, dynamic variable. Exploration of sex variability may uncover both sex differences and sex similarities, but care must be taken in their interpretation. Including females in preclinical research needs to go beyond the investigation of sex differences, improving our knowledge of how this brain region and its subregions mediate behavior and health.

中文翻译：

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啮齿类动物内侧前额叶皮层的性别差异——我们知道什么，不知道什么？

前额皮质，特别是其内侧亚区（mPFC），介导执行控制、行为抑制和记忆形成等关键功能，与日常功能和精神病理学相关。尽管对多种模型生物体中的 mPFC 进行了广泛的表征，但 mPFC 结构和功能根据个体性别而变化的程度尚不清楚——这种知识差距可归因于神经科学研究中对男性受试者的历史偏见。最近将性别视为基础科学中的一个生物变量的努力凸显了缩小这一差距的巨大必要性。在这里，我们回顾了关于雄性或雌性啮齿类动物在 mPFC 神经解剖学、药理学以及招募 mPFC 的厌恶、食欲和目标或习惯导向行为方面如何比较的已知和未知。我们提出，当我们超越仅限男性的研究时，长期存在的 mPFC 结构和功能的教条概念可能不再得到支持，并且有必要对这些教条进行实证挑战。此外，我们还注意到这项工作中的一些常见陷阱。大多数临床前研究将性别作为二元分类，虽然这种方法进一步纳入了非雄性啮齿类动物，但它并不能概括为我们所知道的性别作为多维动态变量。对性别变异的探索可能会揭示性别差异和性别相似性，但在解释它们时必须小心。将女性纳入临床前研究需要超越性别差异的调查，提高我们对这个大脑区域及其子区域如何调节行为和健康的了解。