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


ABSTRACT: 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 (TRAnsneuronal Control of Transcription) 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 Drosophila 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.

SUBMITTER: Huang TH 

PROVIDER: S-EPMC5777821 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (<i>TRACT</i>).

Huang Ting-Hao TH   Niesman Peter P   Arasu Deepshika D   Lee Donghyung D   Lee Donghyung D   De La Cruz Aubrie L AL   Callejas Antuca A   Hong Elizabeth J EJ   Lois Carlos C  

eLife 20171212


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 (<i>TRA</i>nsneuronal <i>C</i>ontrol of <i>T</i>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-engin  ...[more]

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