Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin
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Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin. / Mahn, Mathias; Saraf-Sinik, Inbar; Patil, Pritish; Pulin, Mauro; Bitton, Eyal; Karalis, Nikolaos; Bruentgens, Felicitas; Palgi, Shaked; Gat, Asaf; Dine, Julien; Wietek, Jonas; Davidi, Ido; Levy, Rivka; Litvin, Anna; Zhou, Fangmin; Sauter, Kathrin; Soba, Peter; Schmitz, Dietmar; Lüthi, Andreas; Rost, Benjamin R; Wiegert, J Simon; Yizhar, Ofer.
In: NEURON, Vol. 109, No. 10, 19.05.2021, p. 1621-1635.e8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin
AU - Mahn, Mathias
AU - Saraf-Sinik, Inbar
AU - Patil, Pritish
AU - Pulin, Mauro
AU - Bitton, Eyal
AU - Karalis, Nikolaos
AU - Bruentgens, Felicitas
AU - Palgi, Shaked
AU - Gat, Asaf
AU - Dine, Julien
AU - Wietek, Jonas
AU - Davidi, Ido
AU - Levy, Rivka
AU - Litvin, Anna
AU - Zhou, Fangmin
AU - Sauter, Kathrin
AU - Soba, Peter
AU - Schmitz, Dietmar
AU - Lüthi, Andreas
AU - Rost, Benjamin R
AU - Wiegert, J Simon
AU - Yizhar, Ofer
N1 - Copyright © 2021 Elsevier Inc. All rights reserved.
PY - 2021/5/19
Y1 - 2021/5/19
N2 - 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 Gi/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.
AB - 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 Gi/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.
U2 - 10.1016/j.neuron.2021.03.013
DO - 10.1016/j.neuron.2021.03.013
M3 - SCORING: Journal article
C2 - 33979634
VL - 109
SP - 1621-1635.e8
JO - NEURON
JF - NEURON
SN - 0896-6273
IS - 10
ER -