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 the in vivo mapping of connections between presynaptic and postsynaptic partners in zebrafish, by adapting the trans-Tango genetic approach that was first developed for anterograde transsynaptic tracing in Drosophila. Neural connections were visualized between synaptic partners in larval retina, brain and spinal cord and followed over development. The specificity of labeling was corroborated by functional experiments in which optogenetic activation of presynaptic spinal cord interneurons elicited responses in known motor neuronal postsynaptic targets, as measured by trans-Tango-dependent expression of a genetically encoded calcium indicator or by electrophysiology. Transsynaptic signaling through trans-Tango reveals synaptic connections in the zebrafish nervous system, providing a valuable in vivo tool to monitor and interrogate neural circuits over time. The trans-Tango genetic strategy, which mediates signaling across synapses, was adapted to identify neural connections in a vertebrate nervous system, with synaptic partners confirmed in the retina and spinal cord of larval zebrafish.