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The role of cell adhesion molecules in synaptogenesis in vivo

State/Province Full: 
United States

A current hypothesis for the etiology of autism and other related pervasive disorders points to deficits in the formation of cell to cell contacts during development leading to an imbalance in the triggers that turn cells on and turn cells off. Proper brain development requires precise control of this process to create and maintain complex adult neural networks that can manage multiple types of information at once. Two of the crucial signals which initiate and maintain these neural networks and circuits are called Synaptic cell adhesion molecule (SynCAM) and neuroligin. While previous research supported the importance of Neuroligin and SynCAM in the formation of synapses (biochemical connections between nerve cells), their role in the development of the nervous system has not been well studied or understood. Drs. Washbourne and Pietri will use the zebrafish model to study how neuroligin and SynCAM participate in formation of functional synapses both during development and a behavioral test in the zebrafish called the “touch task”. This test evaluates a motor behavior in response to a sensory stimulus and requires the correct function of both connections which turn on and turn off neuron activity. What this means for people with autism: Independent research has demonstrated that mutations of the neuroligin protein are associated with autism spectrum disorders. This proposal will examine the role of neuroligin and a similar protein, SynCAM, in the development, maintenance, and plasticity of neuronal processes in the brain, notably in respect to changes in neuronal activity. The importance of these two molecules in brain development and connection of neurons can be translated into clinical interventions to directly alter the course of autism spectrum developmental disorders.