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

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Won, Joungha, Pankratov, Yuriy, Jang, Minwoo Wendy, Kim, Sunpil, Ju, Yeon Ha, Lee, Sangkyu, Lee, Seung Eun, Kim, Arie, Park, Soowon, Lee, C. Justin and Heo, Won Do (2022) Opto-vTrap, an optogenetic trap for reversible inhibition of vesicular release, synaptic transmission, and behavior. Neuron, 110 (3). 423-435.e4. doi:10.1016/j.neuron.2021.11.003 ISSN 0896-6273.

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Official URL: https://doi.org/10.1016/j.neuron.2021.11.003

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Brain -- Physiology, Optogenetics , Exocytosis
Journal or Publication Title: Neuron
Publisher: Cell Press
ISSN: 0896-6273
Official Date: 2 February 2022
Dates:
DateEvent
2 February 2022Published
30 November 2021Available
3 November 2021Accepted
17 October 2021Modified
Volume: 110
Number: 3
Page Range: 423-435.e4
DOI: 10.1016/j.neuron.2021.11.003
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Date of first compliant deposit: 12 April 2022
Date of first compliant Open Access: 22 November 2022

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