Dynamic Regulation of Synaptic Function and Development
Our research goal is to understand how synapses develop into functional circuits. Synaptic connections undergo constant fine-tuning to support information delivery and storage in the brain. Regulation of these connections can occur through altering the strength of existing synapses or through synapse assembly and disassembly. We utilize a combination of genetic, biochemical, imaging, and electrophysiological techniques to study the following aspects of synaptic biology.
Synaptic protein dynamics
Synapses are tiny structures that support neurotransmission at high frequency. Protein translocation in and out of synapses plays an important role in shaping synaptic activity. We have developed optical approaches to observe the dynamic behavior of synaptic proteins in living animals (
C. elegans) and to ask how their mobility responds to changes in neuronal activity and developmental cues.Synaptic vesicle endocytosis and its coupling to exocytosis
Neurotransmitter release at synapses occurs by exocytosis of synaptic vesicles (SVs). To maintain neurotransmission, SVs must be regenerated via endocytosis. Stimulation-dependent SV endocytosis is a highly specialized process with unique spatial and temporal controls. Data from our lab and others suggest that components of the endocytic machinery are under direct control of SV exocytosis. We are currently investigating how the key endocytic proteins function and how they are regulated by SV exocytosis.
Synapse Remodeling
Neural circuits undergo an active process of refinement during development and this structural plasticity is thought to underlie brain functions such as learning and memory. During refinement, synaptic connections are reorganized through coordinated events of synapse formation and elimination. Currently, the mechanism by which neurons remodel their synapses is poorly understood. We have identified a transcription factor HBL-1 that regulates remodeling of GABAergic synapses in
C. elegans. We will continue to investigate the molecular pathways defining the timing of synapse remodeling and to identify new genes involved in synapse formation and removal.
