Autism spectrum disorder ASD) is a highly heritable collection of developmental disorders that are typified by difficulties with social interactions, communication deficits and a tendency to engage in repetitive behaviors. Significant research has suggested ASD emerges from an imbalance of excitatory and inhibitory circuit activity within various brain regions yet few molecules have been described that may directly mediate this processes. We are studying a transcription factor called NPAS4, which is expressed in neurons in response to increased excitatory activity. When NPAS4 is expressed, it regulates a set of genes that alter the number and distribution of inhibitory synapses that form on that neuron. Thus, NPAS4 senses excitation and regulates inhibition, acting as a master regulator of excitatory-inhibitory balance.
We are combining optogenetic strategies for activating neurons with whole genome analysis and live imaging to determine how excitatory-inhibitory balance is regulated in a neuron. Our goal is to identify new pathways and molecules that will be therapeutically useful for the treatment of autism and other disorders that emerge from and imbalance of excitation and inhibition.