Won, Joungha Pankratov, Yuriy Jang, Minwoo Wendy Kim, Sunpil Ju, Yeon Ha Lee, Sangkyu Lee, Seung Eun Kim, Arie Park, Soowon Lee, C. Justin Heo, Won Do 2024-01-19T12:33:19Z 2024-01-19T12:33:19Z 2022-04-05 2022-02-02 0896-6273 https://pubs.kist.re.kr/handle/201004/115634 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. English CELL PRESS HIPPOCAMPAL FEAR MEMORY INACTIVATION STIMULATION PERFORMANCE PROJECTIONS ACTIVATION NEURONS CONTEXT Opto-vTrap, an optogenetic trap for reversible inhibition of vesicular release, synaptic transmission, and behavior Article 10.1016/j.neuron.2021.11.003 1 NEURON, v.110, no.3, pp.423 - + NEURON 110 3 423 + scie scopus 000751819100009 2-s2.0-85122918580 Neurosciences Neurosciences & Neurology Article HIPPOCAMPAL FEAR MEMORY INACTIVATION STIMULATION PERFORMANCE PROJECTIONS ACTIVATION NEURONS CONTEXT CIBN CRY2 exocytosis inhibition lariat Opto-vTrap optogenetic inhibition optogenetics vesicular release inhibition