Department of Psychology, Northeastern University, Boston, MA, USA.
Department of Psychology, Northeastern University, Boston, MA, USA.
Neuropharmacology. 2024 May 1;248:109867. doi: 10.1016/j.neuropharm.2024.109867. Epub 2024 Feb 20.
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. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".
前额皮质，特别是其内侧亚区（mPFC），介导了关键功能，如执行控制、行为抑制和记忆形成，与日常功能和精神病理学有关。尽管在多种模式生物中广泛描述了 mPFC，但个体的性别如何影响 mPFC 的结构和功能尚不清楚——这一知识空白可以归因于神经科学研究中对雄性个体的历史偏见。最近，人们努力将性别视为基础科学中的一个生物学变量，突出了弥合这一差距的巨大需求。在这里，我们回顾了关于雄性或雌性啮齿动物在 mPFC 神经解剖学、药理学以及招募 mPFC 的厌恶、奖赏和目标或习惯导向行为方面的异同的已知和未知。我们提出，当我们超越仅雄性研究时，mPFC 结构和功能的长期教条概念可能不再得到支持，并且这些教条的经验挑战是合理的。此外，我们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来操作，虽然这种方法进一步纳入了非雄性啮齿动物，但它并不能推广到我们对性别作为多维、动态变量的了解。对性别变异性的探索可能会揭示性别差异和性别相似性，但在解释时必须小心谨慎。将雌性纳入临床前研究不仅需要调查性别差异，还需要提高我们对大脑区域及其亚区如何介导行为和健康的了解。本文是“精神疾病和相关模型中的 PFC 电路功能”特刊的一部分。
