Synapse Formation

Proper synapse formation in the cerebral cortex during childhood provides the substrate for human perception, learning, memory, and cognition. Conversely, improper formation or function of these synapses leads to many neurodevelopmental disorders, including autism spectrum disorder (ASD) and schizophrenia (SZ; Zoghbi 2003). Despite the importance of synapses for proper functioning of the brain and substantial advances in this field, much remains unknown about the cellular and molecular mechanisms of the formation, stabilization, and elimination of glutamatergic synapses in the CNS.

Results from our lab have provided seminal insights into the cellular mechanisms and molecular signals required for the initial stages of synapse formation, revealing several surprising and novel mechanisms. We are currently studying the effects of activity on synapse formation and the mechanisms of synapse stabilization and elimination using a novel long-term imaging assay we recently developed.

To study synapse dynamics, we employ many techniques—including short-term time-lapse imaging of fluorescently-tagged synaptic proteins during synapse formation and elimination, long-term imaging of synapse stability between neurons expressing fluorescently-tagged pre- and postsynaptic proteins, whole-cell patch-clamp recording, local perfusion and uncaging of molecules at single synapses, biochemistry, electron microscopy, proteomics and genomics. The nature of the mechanistic questions we are interested in requires that we often utilize a reduced model system—cultured cortical neurons—to address these issues.  Our in vitro studies are, however, always complimented by in vivo approaches whenever it is technically feasible.