Overview of Interests
Qi Zhang’s research is focused on how genetic mutation and environmental factors alter synapse formation, or synaptogenesis, and cause developmental disabilities and behavioral problems. Synaptogenesis is an essential process in neuronal development and the plasticity of the neuronal network, and abnormal synaptogenesis is associated with various inborn neurological disorders, including childhood intellectual disability and autism spectrum disorders.
The understanding of many aspects of synaptogenesis, including cell differentiation, migration, and axon guidance, has greatly advanced in recent years, but questions remain regarding synaptic specialization, especially the formation of functional pools of synaptic vesicles in presynaptic terminals and their relationship to the maturation of postsynaptic densities. Recent research has called into question the classic model based on early data, which states that the formation of functional presynaptic terminals precedes the assembly and maturation of postsynaptic densities. Electron microscopy study of tadpoles has shown that pools of synaptic vesicles clustered prior to the axon-dendrite contact, and these findings were later confirmed in other vertebrates, including the mammalian hippocampus. Optical imaging and electrophysiology have also shown that neurotransmitter release often occurs long before outgrowing axons have contacted their targets. It becomes clear that such “orphan” releases of neurotransmitters can shape the dynamic and plastic wiring of neuronal circuits by regulating cell differentiation and the growth of axons and dendrites. It is therefore crucial to understand when and how pools of synaptic vesicles form, release neurotransmitters, and integrate into functional synapses.
Zhang has developed an enzymatic assay to monitor neurotransmitter release, established cell type-specific gene replacement, and invented a nanoparticle-based optical measurement for assessing neuronal communication. By applying these tools to postnatal cultures of rodent neurons, he proposes to elucidate the cellular and molecular mechanisms and abnormalities of synaptogenesis that underly inborn neurological disorders.
View Biographical Sketch (.pdf)