Long-term synaptic plasticity of hippocampal synapses, which is thought to underlie learning and memory formation, requires local translation of proteins. The transcripts used in protein synthesis at the synapse are thought to be released from RNA granules in response to specific stimuli. These granules contain RNA binding proteins and are assembled in the cell soma and transported along dendrites. The neurotrophin BDNF plays a key role in long-term synaptic potentiation in the hippocampus (Prog Neurobiol. 92: 505-516 [2010]; Neuropharmacol 76, 639-656 [2014]), by upregulating protein synthesis at the synapse, in addition to its role in transcription regulation. We are currently investigating the role of BDNF in the modulation of the transport of mRNAs along dendrites and in local translation at hippocampal synapses. Our recent studies showed a key role for the RNA binding protein hnRNP K in the delivery of transcripts used in local protein synthesis at the synapse. This protein mediates the effect of BDNF in the upregulation of the synaptic expression of NMDA receptors which may account, at least in part, for the effects of the neurotrophin in LTP (eNeuro 4: ENEURO.0268-17.2017 [2017]; Science Signal 12: eaav3577 [2019]). In additional studies we are also investigating (i) the role of other neurotrophins in the regulation of the synaptic proteome, and (ii) the role of the FMR1 protein (FMRP) as regulator of translation at the synapse, which is relevant to understand synaptic alterations in Fragile X syndrome, a neurodevelopmental disorder characterized by the absence of FMR1 protein (FMRP). Alterations in synaptic regulation by BDNF is also involved in several disorders of the nervous system. For example, the increased neuronal activity associated with epileptogenesis upregulates the synthesis, expression and release of BDNF, and several pieces of evidence showed a role for BDNF-TrkB signaling is the development of seizures. One of the aims of our work is to understand the molecular mechanisms underlying these effects of BDNF.