Tracing neuronal circuits in transgenic animals by transneuronal control of transcription ( TRACT )

• Published in: eLife Vol. 6
• Main Authors: Huang, Ting-Hao, Niesman, Peter, Arasu, Deepshika, Lee, Donghyung, De La Cruz, Aubrie L, Callejas, Antuca, Hong, Elizabeth J, Lois, Carlos
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 12-12-2017; eLife Sciences Publications, Ltd
• Subjects: Brain; Circadian rhythms; Circuits; connectome; Drosophila; Immunoglobulins; Insects; Ligands; Nervous system; Neural networks; Neurons; Neuroscience; Odorant receptors; Olfactory pathways; Olfactory receptor neurons; Proteins; Proteolysis; synapse; Tools and Resources; Transcription; Transcription factors; Transgenic animals; transneuronal; transsynaptic; wiring; transneuronal; drosophila; neuroscience; transsynaptic; connectome; synapse; D. melanogaster; wiring
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.32027

Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected to one another. We describe a technique called TRACT (
nsneuronal
ontrol of
ranscription) based on ligand-induced intramembrane proteolysis to reveal monosynaptic connections arising from genetically labeled neurons of interest. In this strategy, neurons expressing an artificial ligand ('donor' neurons) bind to and activate a genetically-engineered artificial receptor on their synaptic partners ('receiver' neurons). Upon ligand-receptor binding at synapses the receptor is cleaved in its transmembrane domain and releases a protein fragment that activates transcription in the synaptic partners. Using TRACT in
we have confirmed the connectivity between olfactory receptor neurons and their postsynaptic targets, and have discovered potential new connections between neurons in the circadian circuit. Our results demonstrate that the TRACT method can be used to investigate the connectivity of neuronal circuits in the brain.