The role of Wnt signalling in synaptic maintenance

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The formation of functional synapses, points of contact between two nerve cells (neurons) is crucial for proper brain function. Synapses are very dynamic structures that grow, shrink and change shape through the entire life of the organism. A dialogue between the pre-synaptic neuron (neurotransmitter releasing cell) and its postsynaptic target (a neurotransmitter responding cell) is essential for the formation, growth and maintenance of synapses. Importantly, the formation of new synapses and the remodelling of old ones underlay important functions such as learning and memory. Moreover, recent studies suggest that synaptic loss precedes the death of neurons observed in several neurodegenerative diseases. However, little is known about how synapses are maintained or protected against injury.Our laboratory has been studying the function of secreted factors, called Wnts, in the maintenance of synapses. We found that Wnt blockade induces the loss of mature synapses indicating that Wnts are critical for their maintenance. In this grant proposal, we will examine the molecular mechanism by which Wnts regulate synaptic maintenance and how this process influences neuronal connectivity and animal behaviour. Our results could contribute to the development of therapeutic strategies for the treatment of diseases in which synapses are compromised.