The long-term goal of my research is to understand, from a cell and molecular biological perspective, how mammalian central neurons establish and maintain specific synaptic connections. By establishing these specific synaptic contacts, neurons acquire and process information, a mechanism essential for learning and memory. Recently, I have begun studying the role of different synaptic proteins during the initial phases of neuritic elongation, synaptogenesis and synapse maintenance. In the past two years, my work has focused on the synapsins. The synapsins (synapsin I and synapsin II) are a family of phosphoproteins expressed only in neurons and specifically localized in the presynaptic compartment of the synapses. In the nerve terminals, the synapsins associate with the cytoplasmic surface of synaptic vesicles and bind to the cytoskeleton. We have shown that both synapsin I and II are involved in axonal elongation and branching. In addition, we showed that the synapsins are required for both the formation and maintenance of synapses. Currently we are studying the mechanisms involved in the acquisition of competence to form synapses at the pre and postsynaptic sites.
These studies will provide the basic knowledge needed to analyze the synapse loss associated with neurodegenerative diseases. We are currently investigating the fate of the synapsins and other synaptic proteins under conditions of neuritic degeneration induced by fibrillar beta amyloid.
Our experimental approach involves the use of video-enhanced video microscopy, the generation of null mutations (antisense technology, knockout mice) immunocytochemistry, electron microscopy, protein biochemistry and molecular biology.