FMR1 and fragile X syndrome: The “mGluR theory of FXS” states that the absence of FMRP leads to excessive metabotropic glutamate receptors (mGluRs, mGluR1 and mGluR5) activated long-term depression (LTD) and reduced responsiveness to signals in the hippocampus and other parts of the brain involved in memory and learning.