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Uncovering the role of new synaptic adhesion molecules in encoding synaptic connectivity in the brain (SynapseCode)
Start date: Feb 1, 2013, End date: Jan 31, 2018 PROJECT  FINISHED 

Synapses connect neurons into a network that encodes our thoughts, memories and personalities. Loss of synaptic connectivity is thought to underlie a variety of cognitive disorders such as autism, schizophrenia and Alzheimer’s disease, but little is known about the molecules and mechanisms that establish and maintain the precise patterns of synaptic connectivity in the brain. Neither is it understood how perturbed synaptic connectivity affects cognitive function. The synaptic adhesion molecules that connect pre- and postsynaptic partners across the synaptic cleft provide the key to understand these processes.I hypothesize that the proper formation and function of synaptic connections depends on synapse-specific complexes of adhesion molecules. Together, these complexes form a synaptic adhesion code that specifies synaptic connectivity and contributes to the functional and structural diversity of synapses in the brain. In my preliminary studies, I have identified a large complex of novel synaptic adhesion molecules that is required for normal synapse function, and is ideally suited to confer precise synaptic connectivity. Using in vivo manipulation of these novel synaptic adhesion molecules, I will uncover how the diversity in synaptic adhesion complexes contributes to the specification of synaptic connectivity and the diversity of synapses. Furthermore, I will determine how loss of these novel adhesion molecules affects cognitive function. This will yield new insights in the molecular and cellular mechanisms that underlie the establishment of precise synaptic connectivity in the brain. Ultimately, this insight will guide the development of new strategies for the treatment of cognitive disorders.
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