Opto-vTrap, an optogenetic trap for reversible inhibition of vesicular release, synaptic transmission, and behavior

Spatiotemporal control of brain activity by optogenetics has emerged as an essential tool to study brain function. For silencing brain activity, optogenetic probes, such as halorhodopsin and archaerhodopsin, inhibit transmitter release indirectly by hyperpolarizing membrane potentials. However, these probes cause an undesirable ionic imbalance and rebound spikes. Moreover, they are not applicable to use in non-excitable glial cells. Here we engineered Opto-vTrap, a light-inducible and reversible inhibition system to temporarily trap the transmitter-containing vesicles from exocytotic release. Light activation of Opto-vTrap caused full vesicle clusterization and complete inhibition of exocytosis within 1 min, which recovered within 30 min after light off. We found a significant reduction in synaptic and gliotransmission upon activation of Opto-vTrap in acute brain slices. Opto-vTrap significantly inhibited hippocampus-dependent memory retrieval with full recovery within an hour. We propose Opto-vTrap as a next-generation optogenetic silencer to control brain activity and behavior with minimal confounding effects. [Display omitted] •Opto-vTrap is a quickly reversible optogenetic tool for inhibition of vesicular release•It is a blue-light-induced vesicle-trapping system based on CRY2 and CIBN interaction•It shows reversible inhibition of synaptic and gliotransmission and behavior.•Opto-vTrap can be applied broadly in in vitro, ex vivo, and in vivo models Won et al. engineered Opto-vTrap, a light-inducible and quickly reversible inhibition system to temporarily trap transmitter-containing vesicles from vesicular exocytosis. Opto-vTrap can be used widely in cells, brain slices, and animal behavioral experiments with fast recovery and without affecting membrane potential.