Department of Psychology, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, Bethesda, MD, 20892, USA.
Neuropsychopharmacology. 2022 Nov;47(12):2016-2023. doi: 10.1038/s41386-022-01349-7. Epub 2022 May 26.
The prefrontal cortex (PFC) supports a diversity of cognitive processes. Impairment in PFC-dependent cognition is associated with multiple psychiatric disorders, including those known to display sex differences. Our ability to treat this impairment is limited, in part due to an incomplete understanding of the neural mechanisms that support PFC-dependent cognition. In previous studies in male rats, we demonstrated that corticotropin-releasing factor (CRF) receptors and neurons in caudal dorsomedial PFC (dmPFC) regulate PFC-dependent working memory. Subcortically, CRF can exert sex-specific actions, a subset of which are ovarian steroid dependent. To date, the cognitive actions of dmPFC CRF neurotransmission in females are unknown. To address this gap, the current studies examined the effects of chemogenetic and pharmacological manipulations of CRF receptors and neurons within the dmPFC of female rats tested in a spatial working memory task. Outside of proestrus, activation of both CRF receptors and neurons in the caudal, but not rostral, dmPFC impaired working memory. Meanwhile, blockade of CRF receptors in the caudal dmPFC or globally in the brain, improved working memory performance, similar to that seen in males. In contrast, these effects were not observed during proestrus. These observations demonstrate that while CRF neurotransmission in the PFC regulates working memory similarly in males and females, these actions are not observed in females when ovarian steroids are at peak levels.
前额皮质（prefrontal cortex，PFC）支持多种认知过程。PFC 依赖型认知障碍与多种精神疾病有关，包括那些已知存在性别差异的疾病。我们治疗这种障碍的能力有限，部分原因是我们对支持 PFC 依赖型认知的神经机制了解不完整。在之前对雄性大鼠的研究中，我们证明了促肾上腺皮质激素释放因子（corticotropin-releasing factor，CRF）受体和尾侧背内侧前额皮质（caudal dorsomedial PFC，dmPFC）中的神经元调节 PFC 依赖型工作记忆。在皮质下区域，CRF 可以发挥特定的性别作用，其中一部分作用依赖于卵巢类固醇。迄今为止，dmPFC CRF 神经传递在雌性动物中的认知作用尚不清楚。为了填补这一空白，目前的研究在空间工作记忆任务中检测了化学遗传和药理学操纵雌性大鼠 dmPFC 中的 CRF 受体和神经元对工作记忆的影响。在发情前期之外，激活尾侧但不是头侧 dmPFC 中的 CRF 受体和神经元会损害工作记忆。与此同时，在尾侧 dmPFC 或大脑中全局阻断 CRF 受体，可改善工作记忆表现，与雄性大鼠相似。相比之下，在发情前期观察不到这些作用。这些观察结果表明，虽然 PFC 中的 CRF 神经传递在雄性和雌性中对工作记忆的调节相似，但当卵巢类固醇处于峰值水平时，这些作用在雌性中观察不到。
