"Synapses of the central nervous system are the cellular structures mediating communication between neurons. Mouse mutations studies of synaptic proteins have shown how they ultimately modulate animal cognition and behavior. Furthermore, there is a growing body of data suggesting a central role of the synapse in neurodegenerative, mental and behavioral disorders. This project aims at understanding the synaptic molecular dysfunctions associated with intellectual disorders, particularly non-syndromic intellectual disability (NSID, formerly non-syndromic mental retardation); by doing so it also aspires at learning on the molecular mechanisms behind cognition. The current proposal also attempts at identifying proteins that can become pharmacological targets to treat intellectual disability and to study to what extend mental disorders can be reverted after birth. Mouse models of most synaptic proteins associated with NSID are already available to the scientific community; these will be a key resource to the project. The goal of this research is to study the synapse as a whole biological system and to characterize the changes it undergoes due to disease. That is why proteomics and bioinformatics will be used to quantitatively analyze the synaptic proteome in control and model animals. With the disease-related molecular dysfunctions characterized it might be possible to identify pharmacological targets and to test drugs in the animal models to look for phenotypic recovery. Finally, to investigate the reversibility of NSID, genetic rescue experiments will be performed. These experiments will consist in re-introducing the wild type copy of the gene mutated in the animal model as a conditionally expressed transgene. The transgene expression can be triggered at different developmental stages and the animal recovery can be evaluated for recovery. Identify the developmental stages at where recovery is possible will be key in case pharmacological treatment become available."