Li, N. et al. Elife 8, e48622 (2019).

Babl, S.S. et al. Cell Rep. https://doi.org/10.1016/j.celrep.2019.09.049 (2019).

Optogenetic inhibition is typically achieved by expressing an opsin of choice in the desired target region or across the whole brain, followed by illumination of the brain region of interest. However, inhibition can reach much farther than the illumination volume. Babl et al. and Li et al. have independently examined the spread of optogenetic silencing. Inhibition can be achieved directly by expressing an inhibitory opsin in the neurons of choice or indirectly by expressing channelrhodopsin2 in GABAergic interneurons. The findings suggest that the indirect strategy typically results in more widespread silencing than the direct strategy, and it requires less intense light. Conversely, optogenetic silencing can be confined to smaller areas by using a viral rather than a transgenic expression strategy. The results also showed that direct labeling of neurons with GtACR1, a potent inhibitory opsin, results in silencing as strong as that of the indirect strategy. However, at high light intensities, GtACR1 can have the opposite effect and result in activation, which should be avoided. These studies should provide guidance on which opsins to use in different scenarios.