The genetic causes of intellectual disability (ID) and autism spectrum disorder (ASD) are frequently associated with mutations in genes that encode synaptic proteins. A recent screen of ID patients has revealed that approximately 4% of individuals carry spontaneous autosomal-dominant de novo mutations in the SYNGAP1 gene some of which result in complete absence of the synaptic GTPase activating protein SynGAP (1). Investigations into the pathological consequences of SynGAP haploinsufficiency (Syngap+/−) in mice have reported abnormalities in both behaviour and dendritic spine development. These are analogous to findings from the mouse model of fragile X syndrome (FXS; Fmr1-/y), the most common inherited form of ID. One of the prominent phenotypes reported in the Fmr1-/y mouse is that a form of hippocampal long-term depression (LTD) mediated by the activation of Group 1 (Gp1) metabotropic glutamate receptors (mGluRs) is enhanced and independent of new protein synthesis (2). The cause of these deficits in synaptic plasticity, together with other cognitive abnormalities observed in FXS, are thought to arise in part from an increase in basal protein synthesis, which can be corrected by either inhibiting mGluR5 (3) or reducing Ras and subsequent ERK activity (4). In the present study we examined mGluR-LTD at Schaffer collateral/commissural inputs to CA1 pyramidal neurones in hippocampal slices obtained from Syngap+/− mice. Extracellular field recordings reveal that acute application of the Gp1 mGluR agonist dihydroxyphenylglycine (DHPG; 50 µM) induces a form of mGluR-LTD that is greater magnitude in Syngap+/− mice relative to wild-type (WT) littermate controls (50 µM: 57 ± 7 %, Syngap+/−, n = 14 versus 75 ± 3 %, WT, n = 19). Furthermore mGluR-LTD in Syngap+/− mice is insensitive to protein synthesis inhibitors (unpaired t-test P<0.05, n = 15). In addition, we find basal levels of protein synthesis to be elevated in hippocampal slices fromSyngap+/− mice relative to their WT counterparts (145 ± 15 %, Syngap+/− versus 100 ± 4 %, WT n = 12). The comparable neuropathophysiology we observe between Syngap+/− and Fmr1-/y mice suggests that SynGAP and fragile x mental retardation protein (FMRP) may converge on similar biochemical pathways raising the intriguing possibility that therapeutic strategies used in the treatment of FXS may also be of benefit in treating individuals with ID caused by mutations in SYNGAP.