Investigation of CNS synaptogenesis

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During neuronal development, neuron extends their processes to innervate specific targets. The formation of connections between neurons (called synapses) is essential to establish the architecture of the nervous system. The creation of synapses is also thought to be one of the mechanisms by which learning and memory occur. Recently, in the nervous system, significant progress has been made in identifying molecules responsible for guiding axons to their appropriated target, but the molecules involved in the differentiation of these sites of contact into functional synapses still unknown. Netrins are a family of proteins that have been studied almost exclusively for their role as guidance cues for migrating axons. We recently showed that netrin-1 continues to be present in the nervous system after birth and are enriched at the synapse. These observations led us to investigate a novel function for netrin-1 and its receptors in regulating the formation and the maintenance of new synapses. We have shown that netrin-1 stimulation causes an increase in synapse density. The proposed studies aim to identify the contribution of netrin-1 and its receptors to the formation, remodeling, and maintenance of synapse. Our preliminary findings suggest that we have identified a novel mechanism that plays and important role regulating synaptogenesis during neuronal development and may contribute to synaptic modification in the adult brain. Studying this will contribute to improve our basic understanding of mechanisms that regulate communication between neurons. A better understanding of normal brain functioning will potentially improve our ability to regenerate and reconnect neuron connections lost during neurodegenerative diseases or after traumatic injuries.