Synaptic scaffolding proteins, NMDA receptor function, and autism spectrum disorders

A growing number of synaptic proteins have recently been associated with diverse neuropsychiatric disorders, including autism spectrum disorders (ASDs), schizophrenia, attention deficit hyperactivity disorder, and mood disorders. ASDs represent a group of neurodevelopmental disorders characterized by symptoms, including impaired social interaction and communication and restricted and repetitive interests, behaviors, and activities. Although a large number of ASD-related genetic variations have been identified, only a small number of them have been verified for their causality by approaches including mouse genetics. In addition, neural mechanisms underlying the development of ASDs remain largely unknown. Synaptic scaffolding proteins at excitatory synapses interact with various other proteins including receptors and signaling molecules in order to couple receptor activation with downstream signaling events. In this presentation, I will discuss how defects in some of the excitatory synaptic signaling scaffolds are associated with NMDA receptor dysfunctions and autistic-like behavioral abnormalities in mice.