Molecular Mechanisms that Regulate Central Synapses in Drosophila

Modern neuroscience seeks to understand system-wide connectivity and whole-brain activity as determinants of the complex computations that underlie behavior, thought, and memory. Recent work, though, has revealed that knowledge of three-dimensional synaptic organization is essential to interpret connectivity through the lens of activity and vice versa. To date, synaptic organization in the brain has been less understood due to a lack of techniques to understand the three-dimensional synaptic landscape of an intact circuit. To address this, we have developed light level methods for quantifying synaptic organization in identified classes of neurons in the intact Drosophila brain. I will demonstrate the application of our new methodology, first to understand the basic "rules" that a CNS circuit follows to organize, and second, to describe the essential roles for a number of molecules in enforcing such rules. One such family of molecules, the Teneurins, evolutionarily conserved cell surface proteins, have critical roles at multiple phases of synaptic development via different mechanisms. I will highlight and contrast those specific roles and detail recent work both into Teneurin mechanisms and additional synaptic organizers working in the same system as the Teneurins to ensure proper synaptic organization and development.