Molecular basis of 'synaptopathy' in neurodevelopmental disorders

Abstract

Neurons receive their excitatory synaptic inputs at specialized compartments called dendritic spines, which exist in heterogeneous shapes. The mushroom spines are crucial for memory storage and contain the postsynaptic density (PSD), in which surprisingly large number of proteins accumulate. It is believed that the intricate interactions between diverse proteins in the PSD are essential for the proper maturation and maintenance of dendritic spines. Dysregulation of these proteins can lead to altered dendritic spine development that is closely associated with neurodevelopmental disorders such as autism and intellectual disability. Using a combination of molecular, cellular, electrophysiological and system approaches, I will discuss efforts from my laboratory to delineate the molecular mechanism underlying synapse development, and the link between synaptic defects and altered animal behaviors that are relevant to brain disorders.