Michael E. Greenberg

Our interactions with the outside world trigger changes at neuronal synapses that are critical for brain development and higher cognitive function. Our research has focused on the identification of a genetic program that is activated by neuronal activity, the signal transduction mechanisms that carry the activity-dependent signal from the membrane to the nucleus, and the identification of regulators of this experience-dependent process that affect synapse development and plasticity. We are particularly interested in activity-dependent processes whose dysfunction can lead to the development of human diseases of cognition such as autism and mental retardation.Using global screening techniques to identify proteins whose activity is regulated by stimuli such as membrane depolarization and calcium influx in neurons, we have identified a number of genes that regulate processes such as dendritic arborization, spine development, protein interactions, local control of protein translation at the synapse by micro-RNAs, and the relative number of excitatory and inhibitory synapses. Many disorders of cognition are correlated with changes in the number of synapses or an imbalance between excitation and inhibition in the nervous system. Thus, understanding the activity-dependent mechanisms that govern synaptic development may reveal how the deregulation of this process leads to neurological diseases.