Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system

Wnts are evolutionarily conserved secreted glycoproteins that contribute to the patterning and development of many tissues in C. elegans, Drosophila and mammals. In the nervous system, Wnt signaling contributes to postmitotic cell fate, axon pathfinding, synaptogenesis and synaptic function. However, as we discuss here, the role of Wnt signaling is not limited to the development of the nervous system, as it also has an ongoing role in the modulation of synaptic strength by experience. Indeed, disrupted Wnt signaling has been implicated in a variety of neurological disorders, such as Alzheimer disease, schizophrenia and depression, all of which are associated with altered synaptic function. In all nervous systems, networks of interconnected neurons process information at specialized points of contact called synapses. At these specializations, neurotransmitter released from the presynaptic membrane of one neuron binds to receptors localized to the postsynaptic membrane of the apposed neuron. The strength of transmission between neurons is modulated by experience-dependent changes at synapses. These dynamic processes—especially changes in the number of functional receptors at the postsynaptic membrane—are believed to underlie learning and memory. Elegant genetic studies in Drosophila larvae and in C. elegans have demonstrated that Wnt signaling can modify the structure and function of developing synapses. In mammals, application of exogenous Wnts has diverse effects on developing neurons, including preand post-synaptic differentiation, changes in spine density and on the endocytosis and recycling of neurotransmitter receptors. Together, these studies raise the question Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system