[
International Worm Meeting,
2021]
The architecture of the developing brain is highly dynamic with new synapses appearing as others are removed. Despite the key role of synaptic plasticity in sculpting circuit function, little is known of the molecular pathways that determine whether a synapse will be eliminated or maintained during development. To address this question, we are studying synaptic remodeling in GABAergic Dorsal D (DD) motor neurons in C. elegans. DD synaptic remodeling involves the translocation of ventral presynaptic DD terminals to the dorsal side during early larval development. Although DD remodeling was originally discovered by EM reconstruction, dynamic imaging methods with fluorescently labeled synaptic markers are more readily implemented for temporal studies of the underlying cell biological mechanisms. To circumvent the potential problem of over-expression from transgenic arrays, we are testing an endogenously labeled presynaptic marker, GFP::RAB-3. Because it is closely associated with synaptic vesicles, RAB-3 is a reliable marker for the presynaptic apparatus. In this case, we are using cell-specific flippase to limit GFP::RAB-3 expression to DD neurons. From snapshots of GFP::RAB-3 at five different time points in late L1 early L2 C. elegans larvae, we have confirmed that DD presynaptic domains are eliminated from the ventral side as new dorsal GFP::RAB-3 puncta emerge. We are now using our native GFP::RAB-3 marker to screen candidate genes for roles in the DD remodeling program. The long-term goal of this work is to identify remodeling genes that also govern synaptic plasticity in the human brain.