Subtle changes in the molecular organization of synapses may profoundly affect synaptic transmission and animal behavior. Yet, neural systems and animals behave robustly for a lifetime, implying a tight homeostatic regulation of the molecular architecture of synapses. Recent evidence suggests a sub-synaptic molecular organization at the nanometer scale that is trans-synaptically aligned between synaptic compartments. The molecular mechanisms that establish and regulate this transsynaptic nano-architecture are largely unknown.
The central goal of this project is to explore the molecular mechanisms controlling trans-synaptic nano-architecture and its homeostatic modulation.
This project is based on the discovery of trans-synaptically-aligned nano-rings of synaptic proteins that undergo rapid changes during homeostatic plasticity at the Drosophila neuromuscular junction. We are currently systematically investigating trans-synaptic nano-architecture after genetic perturbation of synaptic proteins using super resolution light microscopy approaches.