Optogenetics, the use of light ­driven microbial opsins to mediate optical control of neuronal activity, is in widespread use for the activation and silencing of populations of neurons. Natural neural codes, however, vary from neuron to neuron even within a single class of cells, with the firing of even single neurons capable of altering behavior or brain state. Thus, an intriguing question is whether it is possible to drive individual neurons. In recent years, two ­photon (2P) photostimulation of individual neurons expressing optogenetic proteins has begun to be explored. 2P activation is essential for selective targeting of single neurons because it excites opsins precisely where the light is aimed, unlike single photon stimulation wherein the stray light would activate opsin-­bearing neurons away from the targeted cell. Of the different 2P stimulation approaches, computer generated holography (CGH) stands out since it enables precise sculpting of the illumination volume and simultaneous illumination of an entire cell or even multiple cells at the same time. Holography also enables millisecond temporal resolution and even sub­millisecond temporal jitter of action potential generation, meaning that CGH could support single cell, sub­millisecond optogenetic control. Despite recent advances in 2P stimulation, there remains a major problem. In a neuronal network, cell bodies are densely surrounded by neurites of neighboring cells. Thus, if neurons within a region are bearing densely expressed opsins, even 2P stimulation of a single neuron’s cell body may excite opsins on dendrites or axons that are passing by, causing artifactual activation of nearby neurons. To avoid this crosstalk, we designed a soma ­targeted opsin, which is selectively expressed in the cell  body. We screened for soma targeting proteins and found a protein fragment that could limit GFP expression to the cell body of neurons. We termed this fragment ‘SomaTag’, and fused to it the powerful channelrhodopsin CoChR. We found SomaTag­CoChR to localize to the cell body of neurons in the mammalian cortex, and in combination with holographic 2P stimulation, could support optogenetic stimulation of single cells in mammalian brain slices with millisecond temporal resolution. This new SomaTag-­CoChR, in conjunction with optimized 2P optics, may enable a diverse set of neural codes and computations to be probed in a causal fashion in systems and circuit neuroscience.