Synaptic Mechanisms underlying Phelan McDermid and Asperger's Syndrome

Project Leader: Craig Garner e-mail


Autism spectrum disorders (ASDs) have risen to approximately 1 in 88 over the past years, affecting an entire generation of children, families and communities. Currently, the diagnosis for most forms of ASD is based on a triad of behavioral symptoms, including social impairments, communication difficulties, and repetitive or stereotyped behaviors, with no quantitative measures for screening or assessment of potential drug therapies. Electrophysiological measurements of synapses/neuronal networks from monogenic forms of ASD hold the potential for understanding mechanism and developing new treatment strategies. To gain better insights into how ASD associated mutations in synaptic proteins adversely affect synaptic transmission and plasticity, we propose studies to test a novel hypothesis that excitatory synapses use a zinc sensitive signaling pathway to regulate pre/postsynaptic coupling and thus the establishment of long-lasting changes in synaptic strength. This will be accomplished by performing a combination of dynamic imagining and paired cell electrophysiological recording from hippocampal neurons in culture to define how ASD associated mutations in Shank3 impair pre/postsynaptic coupling, synaptic maturation and neuronal network function.