Journal
NEURON
Volume 109, Issue 10, Pages 1621-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2021.03.013
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Funding
- European Research Commission (ERC) [819496, 714762]
- Israel Science Foundation [COEX 3131/20]
- Adelis Brain Research Award
- Ilse Katz Institute for Material Sciences and Magnetic Resonance Research
- EMBO [ALTF 352-2019, ALTF 914-2018, ALTF 378-2019]
- Achar Research Fellow Chair in Electrophysiology
- Minerva Foundation
- German Research Foundation (DFG) [FOR2419, SFB936, EXC-2049, SFB 958, SFB 1315, SFB 1665, SPP 1926]
- European Research Council (ERC) [819496, 714762] Funding Source: European Research Council (ERC)
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A mosquito homolog of vertebrate encephalopsin was found to effectively suppress synaptic transmission through a specific signaling pathway, triggering lasting synaptic output inhibition that recovers spontaneously in vitro and in vivo. This discovery opens up new avenues for functional exploration of long-range neuronal circuits in vivo.
Information is carried between brain regions through neurotransmitter release from axonal presynaptic terminals. Understanding the functional roles of defined neuronal projection pathways requires temporally precise manipulation of their activity. However, existing inhibitory optogenetic tools have low efficacy and off-target effects when applied to presynaptic terminals, while chemogenetic tools are difficult to control in space and time. Here, we show that a targeting-enhanced mosquito homolog of the vertebrate encephalopsin (eOPN3) can effectively suppress synaptic transmission through the G(i/o) signaling pathway. Brief illumination of presynaptic terminals expressing eOPN3 triggers a lasting suppression of synaptic output that recovers spontaneously within minutes in vitro and in vivo. In freely moving mice, eOPN3-mediated suppression of dopaminergic nigrostriatal afferents induces a reversible ipsiversive rotational bias. We conclude that eOPN3 can be used to selectively suppress neurotransmitter release at presynaptic terminals with high spatiotemporal precision, opening new avenues for functional interrogation of long-range neuronal circuits in vivo.
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