Along this project, we have explored the alterations of the glutamatergic synapse of the Ts65Dn mouse model of Down syndrome. We have fully characterized the proteomic and phosphoproteomic profile of subsynaptic fractions of the hippocampi of trisomic mice. Along this approach, we characterized candidate residues of the glutamate ionotropic receptors that are altered in trisomic mice.
Further, we have analyzed the functional consequences (synaptic morphology, electrophysiology) of this aberrant phosphopattern, which allowed us to understand the contribution of the glutamatergic neurotransmission alterations in Down syndrome etiology. Overall, the data accumulated along this project strongly support the alteration of the glutamatergic transmission in Down syndrome, which can be defined as a therapeutic target for further pharmacological interventions.