4.7 Review

Optogenetics at the presynapse

Journal

NATURE NEUROSCIENCE
Volume 25, Issue 8, Pages 984-998

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41593-022-01113-6

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Funding

  1. Deutsche Forschungsgemeinschaft (DFG
  2. German Research Foundation) [SPP 1926, EXC-2049-390688087, SPP 1665, SFB 1315, SFB 958]
  3. European Research Commission (ERC CoG PrefrontalMap) [819496]
  4. Israel Science Foundation [ISF 3131/20]
  5. EMBO [ALTF 378-2019]
  6. Amos de Shalit-Minerva fellowship
  7. Joseph and Wolf Lebovic Charitable Foundation Chair for Research in Neuroscience
  8. European Research Commission (H2020-RIA DEEPER) [101016787]
  9. European Research Commission (ERC SyG BrainPlay) [810580]
  10. European Research Council (ERC) [819496, 810580] Funding Source: European Research Council (ERC)

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This review provides a comprehensive overview of the presynaptic applications of optogenetic tools, discussing the challenges, limitations, and future directions. Optogenetic actuators enable precise control of presynaptic functions, such as light-mediated neurotransmitter release, presynaptic inhibition, induction of synaptic plasticity, and manipulation of individual components of the presynaptic machinery.
This Review provides a comprehensive overview of presynaptic applications of optogenetic tools, including the associated challenges, current limitations and future directions for this approach. Optogenetic actuators enable highly precise spatiotemporal interrogation of biological processes at levels ranging from the subcellular to cells, circuits and behaving organisms. Although their application in neuroscience has traditionally focused on the control of spiking activity at the somatodendritic level, the scope of optogenetic modulators for direct manipulation of presynaptic functions is growing. Presynaptically localized opsins combined with light stimulation at the terminals allow light-mediated neurotransmitter release, presynaptic inhibition, induction of synaptic plasticity and specific manipulation of individual components of the presynaptic machinery. Here, we describe presynaptic applications of optogenetic tools in the context of the unique cell biology of axonal terminals, discuss their potential shortcomings and outline future directions for this rapidly developing research area.

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