Stauffer, W.R. et al. Cell 166, 1564–1571 (2016).

Optogenetic activation is a powerful method for unraveling the functions of different cell types in the brain. However, achieving cell type specificity is challenging in organisms that are difficult to manipulate genetically. Stauffer et al. describe an approach for optogenetic stimulation of dopamine neurons in the macaque brain with high specificity and efficiency. The researchers injected two viruses into the target brain region: one that expresses Cre recombinase under the control of a promoter fragment specific for dopamine neurons, and one that harbors a Cre-dependent channelrhodopsin construct. This strategy allowed them to avoid the low expression levels often associated with direct promoter-fragment-driven expression of effector proteins. The researchers applied their approach to activate dopamine neurons in the macaque midbrain and studied the targeted neurons using electrophysiology and behavioral experiments.