Transsynaptic labeling and transcriptional control of zebrafish neural circuits

Deciphering the connectome, the ensemble of synaptic connections that underlie brain function, is a central goal of neuroscience research. Here, we report mapping of connections between presynaptic and postsynaptic partners in a living vertebrate nervous system, that of the zebrafish, through the successful adaptation of the trans -Tango genetic approach, first developed for anterograde transsynaptic tracing in Drosophila . Neural connections were visualized between synaptic partners in the larval retina and brain and followed over development. Results were corroborated by functional experiments in which optogenetic activation of retinal ganglion cells elicited responses in neurons of the optic tectum, as measured by trans -Tango-dependent expression of a genetically encoded calcium indicator. Transsynaptic signaling through trans -Tango reveals predicted as well as previously undescribed synaptic connections in the zebrafish brain, providing a valuable in vivo tool to monitor and interrogate neural circuits over time.