PRESERVED NAVIGATION WITH ALTERED REWARD-MODULATED RAMPING ACTIVITY IN MEDIAL ENTORHINAL CORTEX IN FRAGILE X MICE

Fragile X Syndrome (FXS), a monogenetic cause of autism spectrum disorders resulting from mutations in the FMR1 gene, is associated with impairments in spatial cognition. While previous work has primarily focused on hippocampal abnormalities, far less is known about how FXS affects the medial entorhinal cortex (MEC). In this study, we investigated MEC neural dynamics in Fmr1 knockout mice using tetrode recordings during spatial navigation on linear tracks with reward-based learning in visual reality (VR). We found that FXS mice performed similarly to wild-type (WT) controls in remembering reward locations, adapting to changes in reward position, and flexibly switching between track contexts with different reward locations, both with and without visual cues marking the reward zone. To compare MEC neural activity across genotypes, we focused on a specific functional cell type called ramping cells defined by changes in firing rate before and after the reward zone (Tennant et al., 2022, https://doi.org/10.1016/j.cub.2022.08.050). FXS and WT mice showed robust differences in ramping cell firing rate profiles (Figure 1). The offset was largely independent of animal’s distance to the reward zone, and its magnitude and direction varied across ramping cell subtypes and trial types. We hypothesised that the ramping cell subtypes may relate to different types of interneurons, which have been shown to display similar activity patterns in the hippocampal CA1. These results show that, despite similar navigation performance, FXS mice exhibited altered reward-modulated MEC ramping cell activity, which may affect grid cell network dynamics and will be unravelled in future work.