Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 44, Pages 10679-10689Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1246-17.2017
Keywords
holography; optogenetics; two-photon excitation
Categories
Funding
- Agence Nationale de la Recherche [ANR-10-INBS-0401, ANR-14-CE13-0016]
- National Institute of Health [1-U01-NS090501-01]
- Getty Lab
- Medical Research Foundation [DVS20131228920]
- Federation pour la Recherche sur le Cervau (FRC)
- Rotary Club through the program Espoir en Tete
- Human Frontier Science Program [RGP0015/2016]
- National Science Foundation International Postdoctoral Research Fellowship
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Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity relate causally to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon (2P) light-targeting strategies demonstrated in-depth generation of action potentials in photosensitive neurons both in vitro and in vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events. Here, we show that efficient current integration enabled by 2P holographic amplified laser illumination of Chronos, a highly light-sensitive and fast opsin, can evoke spikes with submillisecond precision and repeated firing up to 100 Hz in brain slices from Swiss male mice. These results pave the way for optogenetic manipulation with the spatial and temporal sophistication necessary to mimic natural microcircuit activity.
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