Grant: Project Grant

Nerve cell connections, known as synapses, are the fundamental units of communication and information processing in the brain. Synapses develop by interactions of specialized proteins called synapse organizers. We now show that these proteins are not only required for synapse organization but are also required for enduring changes in synapses that are important for cognitive functions such as learning and memory. Variations in the genes for major synapse organizing proteins predispose to neuropsychiatric disorders such as autism and schizophrenia. We have discovered a novel form of a disease-associated synapse organizing protein abundant in the brain but whose function is entirely unknown. We have discovered that an intricate biochemical switch governs the binding of this class of synapse organizers to its cognate partners essential for their function. In a mouse brain circuit, we will explore how synapses develop and function when this switch is turned on or off and assess how this affects the underlying process leading to learning and memory. Our work will show how altered biochemical signaling affects brain wiring, producing deficits such as in autism and schizophrenia. Our study will increase our understanding of the causes of neuropsychiatric disorders and enable us to identify amenable targets to design rational drugs for neuropsychiatric disorders.