Visual capture of the head-direction signal in a rat model of Fragile X Syndrome

Fragile X Syndrome (FXS) is a common inherited monogenic cause of autism spectrum disorder and intellectual disability (ASD/ID), conditions frequently associated with altered sensory processing and multisensory integration. However, the circuit mechanisms underlying these alterations remain poorly understood. Here, we investigate the integration of visual and self-motion information in the head-direction (HD) system in a rat model of FXS ( Fmr1 -/y rats). Using high-density silicon probes, we recorded neuronal activity in the postsubiculum (PoSub), a cortical hub of the HD system, while adult Fmr1 -/y and wild-type (WT) rats experienced repeated rotations of a visual landmark. In WT rats, the HD signal only partially followed landmark rotations, consistent with weighted integration of visual and self-motion information, and visual landmark control progressively weakened across repeated cue conflicts. In contrast, the HD signal in Fmr1 -/y rats closely followed landmark rotations and failed to show experience-dependent recalibration. This enhanced visual capture was accompanied by reduced angular head velocity tuning in PoSub neurons, indicating weakened representation of self-motion information. Together, these findings reveal an altered balance between visual and self-motion inputs to the HD system in a rat model of FXS and identify a possible circuit-level mechanism through which sensory integration of vision and self-motion may be disrupted in ASD/ID.