The role of Wnt signalling in excitatory hippocampal synapse formation and function

摘要: The formation of a functional neural network is dependent on the correct assembly cell-cell contacts. Apposition pre and post synaptic terminals highly regulated process culminating in the functional junction points called synapses. Whilst much understood processes involved bringing axon target together less mechanisms controlling synapse maintenance. Wnts are glycosylated secretary proteins which have been demonstrated to be at several stages of developing nervous system. Through range signalling pathways Wnts able produce cellular effects including embryonic patterning, fate movement. Much recent research has focused role of function. In this thesis I present data from hippocampal cultures showing Wnt7a regulation excitatory synapses. Exposure neurons results an increase density surface GluA1, GluA2 GluN1 puncta dendritic spines. also regulates co-localisation postsynaptic glutamate receptor with presynaptic sites labelled vesicular glutamate transporter protein (vGlut). Interestingly the mediated no longer mature cultures. At main site transmission identified Dvl mediated maturation glutamatergic receptor localisation. Both exogenous overexpression 14DIV hippocampal caused size number located spines the proportion containing GluA1, GluA2 puncta. In my vivo functional data, using animals null for both expression. These demonstrate defects evoked post synaptic currents paired pulse ratio CA3-CA1 synapse. In conclusion report demonstrates crucial role – excitatory synapse hippocampus. Furthermore amongst myriad ways Wnt7a-Dvl signalling affects development CNS, acts directly strength.