CA2 neurons show abnormal responses to social stimuli in a rat model of Fragile X syndrome

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 (Fmr1 knockout rats). In Fmr1 knockout rats, we observed impaired CA2 cell responses to social stimuli, despite similar social behaviors. Further, in CA2 of Fmr1 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. Significance statementFragile 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.