Trimper, J. B. | Search bioRxiv

bioRxiv2025

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.

neuroscience↗

bioRxiv2017

Grid cell co-activity patterns during sleep reflect spatial overlap of grid fields during active behaviors

Continuous attractor network models of grid formation posit that recurrent connectivity between grid cells controls their patterns of co-activation. Grid cells from a common module exhibit stable offsets in their periodic spatial tuning curves across environments, which may reflect recurrent connectivity or correlated sensory inputs. Here we explore whether cell-cell relationships predicted by attractor models persist during sleep states in which spatially informative sensory inputs are absent. We recorded ensembles of grid cells in superficial layers of medial entorhinal cortex during active exploratory behaviors and overnight sleep. Per pair and collectively, we found preserved patterns of spike-time correlations across waking, REM, and non-REM sleep, which reflected the spatial tuning offsets between these cells during active exploration. The preservation of cell-cell relationships across states was not explained by theta oscillations or CA1 activity. These results suggest that recurrent connectivity within the grid cell network drives grid cell activity across behavioral states.

neuroscience↗