In comparison to WT CA3 neurons (left side), FXS neurons (right side) show a hyperabundance of long and thin dendritic spines in the stratum radiatum (right upper tile). Given the fact that FMRP has an important function in mRNA transport and the regulation of local translation, our work suggests that this phenotype might be based on altered actin dynamics, caused by a dysregulation of actin‐binding proteins (ABPs) (right upper tile, here shown for the ABPs profilin 1 (PFN1) and cofilin 1 (CFL)). Surprisingly, we found mossy fibre synapses on CA3 neurons in the stratum lucidum (lower tiles) to be structurally altered as well, having increased numbers of thorny excrescences (TE), containing more surface AMPA receptors as well as more clusters of the ABP synaptopodin.