Enhanced mGluR-LTD in the absence of FMRP has given rise to the mGluR hypothesis of FXS; higher hippocampal (mGluR-dependent) LTD in Fmr1 knockout mice no longer shows a requirement for protein synthesis (as the normal control on protein synthesis mediated by FMRP is lost). This evidence concerns the gene FMR1 and fragile X syndrome.