The role of FMRP in translation-dependent synaptic plasticity. (A) FMRP and mGluR5 impose opposite regulation on the local mRNA translation required for mGluR-LTD expression. In the absence of FMRP, there is excessive protein synthesis and exaggerated LTD. (B) While FMRP is known to regulate the translation required for LTD, evidence suggests it is not involved in the expression of L-LTP. There may be different pools of mRNA available at the synapse that are differentially required for LTD versus LTP, and FMRP may specifically regulate the pool required for LTD. (C) FMRP is explicitly involved in the regulation of dendritically localized translation and may not regulate somatic translation. Consequently, FMRP may only impact forms of plasticity that require local translation, such as mGluR-LTD. (D) In addition to mGluR-LTD, FMRP regulates the protein synthesis involved in mGluR-dependent facilitation of LTP. This finding suggests that the proteins whose translation is controlled by FMRP may be involved in bi-directional maintenance of plasticity rather than being specific to LTD.