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

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Monday, 2 October 2017

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

Ronzitti E, et al. J Neurosci. 2017.

J Neurosci. 2017 Oct 2. pii: 1246-17. doi: 10.1523/JNEUROSCI.1246-17.2017. [Epub ahead of print]

Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity causally relate 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 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 two-photon 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.


To reveal causal links between neuronal activity and behavior, it is necessary to develop experimental strategies to induce spatially and temporally sophisticated perturbation of network microcircuits.

Two-photon computer generated holography (2P-CGH) recently demonstrated three-dimensional optogenetic control of selected pools of neurons with single-cell accuracy in-depth in the brain.

Here we show that exciting the fast opsin Chronos with amplified laser 2P-CGH enables cellular-resolution targeting with unprecedented temporal control, driving spiking up to 100 Hz with submillisecond onset precision, using low laser power densities.

This system achieves a unique combination of spatial flexibility and temporal precision needed to optogenetically pattern inputs that mimic natural neuronal network activity patterns.

Copyright © 2017 the authors.
PMID: 28972125 [PubMed - as supplied by publisher]