Transsynaptic mapping and manipulation of neural circuits in flies by trans-Tango - Gilad Barnea

Gilad Barnea, PhD

Doctors Fox Associate Professor of Ophthalmology, Visual Science, and Neuroscience
Brown University

Host: Ethan Richman (Deisseroth/Luo Lab)

Abstract

I will present trans-Tango, a new technique for anterograde transsynaptic circuit tracing and manipulation that we have established in fruit flies. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell-surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners. Activation of the pathway culminates in expression of a reporter that can be visualized. Because our system is modular, it can be easily adapted to experiments in which the properties of specific circuits are modified and the functional consequences are analyzed. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the firstorder receptor neurons are not well characterized. We identified second-order neurons within the sweet and bitter circuits and revealed that they target brain areas involved in neuromodulation with similar but distinct projection patterns. Using our studies in flies as proof of concept, we are currently establishing an equivalent technique for labeling circuits in vertebrate models, such as mice and zebrafish. These experiments establish trans-Tango as a flexible platform for comprehensive transsynaptic analysis of neural circuits.

Curriculum Vitae

Website

Related Papers

[1] Gilad Barnea, Walter Strapps, Gilles Herrada, Yemiliya Berman, Jane Ong, Brian Kloss, Richard Axel, and Kevin J. Lee. The genetic design of signaling cascades to record receptor activation. PNAS January 8, 2008 105 (1) 64-69. DOI: 10.1073/pnas.0710487105

[2] Mustafa Talay, Ethan B. Richman, Nathaniel J. Snell, Griffin G. Hartmann, John D. Fisher, Altar Sorkaç, Juan F. Santoyo, Cambria Chou-Freed, Nived Nair, Mark Johnson, John R. Szymanski, Gilad Barnea. Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango. Neuron. 2017 Nov 15;96(4):783-795.e4. doi: 10.1016/j.neuron.2017.10.011. Epub 2017 Oct 26. DOI: 10.1016/j.neuron.2017.10.011