Figure 2. Targeting optogenetic tools in vivo. (Top) Direct stimulation of neuronal cell bodies is achieved by injecting virus at the target region and then implanting a light-delivery device above the injected region. Even this simple experiment can provide specificity with viruses that will not transduce afferent axons and fibers of passage. Additional cell-type specificity is attained either by cell-type-specific promoters in the viral vector or via a recombinase-dependent virus, injected in a transgenic animal expressing a recombinase such as Cre in specific cells, leading to specific expression of the transgene only in defined cell types. (Bottom) Projection (axonal) targeting is achieved by viral injection at the region harboring cell bodies, followed by implantation of a light-delivery device above the target region containing neuronal processes from the virally transduced region; in this way, cell types are targeted by virtue of their projections. Reproduced from reference 19: Tye KM, Deisseroth K. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci. 2012;13(4):251-266. Copyright © Nature Publishing Group, 2012. Originally published in reference 20: Yizhar O, Fenno LE, Davidson TJ, Mogri M, Deisseroth K. Optogenetics in neural systems. Neuron. 2011;71(1):9-34. Copyright © Elsevier, Inc. 2011.