Sub-millisecond optogenetic control of neuronal firing with two-photon holographic photoactivation of Chronos

• Main Authors: Ronzitti, E. (Author), Conti, R. (Author), Zampini, V. (Author), Tanese, D. (Author), Foust, A.J (Author), Papagiakoumou, E. (Author), Emiliani, V. (Author), Klapoetke, Nathan Cao (Contributor), Boyden, Edward (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), Massachusetts Institute of Technology. Media Laboratory (Contributor), McGovern Institute for Brain Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Society for Neuroscience, 2018-05-09T15:57:49Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (Grant 1-U01-NS090501-01)