Dissecting synaptic organisation
Formation of neuronal synapses is a complex process that involves precise interaction of cells, formation of synaptic connections and correct localisation of proteins. This complexity has hampered the full delineation of the proteins involved and their interplay. Seeking to address this issue, the EU ‘Synaptic scaffolding proteins orchestrating cortical synapse organisation during development’ (Synscaff) project worked to unravel the complex molecular mechanisms driving synaptic structuring and organisation during development of cortical networks and circuitries. The ultimate aim was to reach a more comprehensive understanding of cortical networking during development and in particular of genes and their products governing these processes. Scientists characterised the role of known and new pre-synaptic and post-synaptic proteins in synapse formation and synaptic function in vitro and in animal models. The Synscaff project also looked at the impact of key genes ruling excitatory synaptic function in mental retardation. This was achieved by mutating genes and generating transgenic animals for scaffolding proteins, as well as for key elements in mental retardation. Subsequent molecular, electrophysiological and behavioural analysis resulted in the identification of novel developmental steps implicated in mental retardation. Project findings contributed significant knowledge on the assembly and function of the excitatory synapse, improving our understanding on how signal transmission is regulated in health and disease. Furthermore, exploitation of the Synscaff results has already resulted in the commercial production of antibodies which are now available to the scientific community.