Donahue Margaret M, Robson Emma, Marron Alyssa M, Fernandez Edel J, Hill Misty, Mably Alexandra J, Trimper John B, Brager Darrin H, Colgin Laura Lee
bioRxiv. 2025 Sep 11:2025.09.10.674743. doi: 10.1101/2025.09.10.674743.
Fragile X Syndrome (FXS) is a neurodevelopmental disorder that is highly comorbid with autism spectrum disorders and can cause abnormal social behaviors. The CA2 subregion of the hippocampus is essential for social memory processing and social recognition. A social interaction induces changes in CA2 neuronal firing; however, it is unknown whether these changes are impaired in FXS models. Here, we examined CA2 activity in a rat model of Fragile X Syndrome ( knockout rats). In knockout rats, we observed impaired CA2 cell responses to social stimuli, despite similar social behaviors. Further, in CA2 of knockout rats, we found reduced expression of oxytocin receptors and impaired whole cell responses to oxytocin. Together, these results raise the possibility that abnormal CA2 activity contributes to impaired social behavior in FXS and may suggest novel treatment targets for FXS patients.
Fragile X Syndrome (FXS) is a neurodevelopmental disorder that can result in abnormal social behaviors, including social avoidance. Activity in the CA2 subregion of the hippocampus is believed to support social recognition and social cognition. Yet, the extent to which the CA2 subregion of the hippocampus is affected by FXS is poorly understood. In this study, we identified specific impairments in CA2 neuronal responses to social stimuli in a rat model of FXS. Further, we provide evidence suggesting that CA2 responses to oxytocin, a neuropeptide released during social interactions, are abnormal in FXS.
脆性X综合征（FXS）是一种神经发育障碍，与自闭症谱系障碍高度共病，可导致异常社交行为。海马体的CA2亚区对于社会记忆处理和社会认知至关重要。社会互动会引起CA2神经元放电的变化；然而，在FXS模型中这些变化是否受损尚不清楚。在这里，我们检查了脆性X综合征大鼠模型（敲除大鼠）中的CA2活性。在敲除大鼠中，尽管社交行为相似，但我们观察到CA2细胞对社会刺激的反应受损。此外，在敲除大鼠的CA2中，我们发现催产素受体表达降低，并且对催产素的全细胞反应受损。总之，这些结果增加了异常CA2活性导致FXS社交行为受损的可能性，并可能为FXS患者提示新的治疗靶点。
脆性X综合征（FXS）是一种神经发育障碍，可导致异常社交行为，包括社交回避。海马体CA2亚区的活动被认为支持社会认知和社会认知。然而，人们对FXS对海马体CA2亚区的影响程度了解甚少。在这项研究中，我们在FXS大鼠模型中确定了CA2神经元对社会刺激反应的特定损伤。此外，我们提供的证据表明，在FXS中，CA2对催产素（一种在社会互动过程中释放的神经肽）的反应是异常的。
