Fragile X syndrome is the most common form of inherited intellectual disability and a major cause of autism spectrum disorder. This syndrome is caused by the silencing of the Fmr1 gene, which codes for the RNA-binding protein, FMRP. Most studies have focused on dendritic and postsynaptic mechanisms. Here we aim at characterising the functional involvement of new FMRP targets by exploring the consequences of FMRP loss on presynaptic mechanisms. We focus in particular on a recently identified target, Phosphodiesterase 2A (PDE2A). PDE2A is located in the presynaptic compartment and is highly expressed in the brain regions involved in this pathology. We have studied how the absence of FMRP selectively in the dentate gyrus (DG) granule cells and the consequent deregulation of the PDE2A protein affects presynaptic mechanisms at hippocampal mossy fiber synapses onto CA3 pyramidal cells. We use a combination of patch-clamp electrophysiology, optogenetics and two-photon imaging on acute and organotypic slices in mice with selective genetic mutations in DG granule cells. We show that the deletion of FRMP in DG granule cells does not significantly affect their intrinsic spiking properties; however we provide evidence for distinctive alterations in presynaptic mechanisms (including initial release probability) and short-term plasticity. Pharmacological intervention on cAMP-dependent synaptic mechanisms appear impaired, suggesting that ourresults may be interpreted as a deregulation of protein kinase A, activated by cAMP. These promising results are currently complemented by an analysis of the dynamics of cAMP at the presynaptic level, using a biosensor for cAMP and biphoton microscopy in slices.