A new fluorescent protein highlights active nerve cells across the brains of animals, allowing researchers to look for neural circuits that process environmental cues or control certain behaviors (Science 2015, DOI: 10.1126/science.1260922). Eric R. Schreiter of the Janelia Farm Research Campus and colleagues developed the protein so that it senses spikes in calcium ion concentration inside cells, a sign that a neuron has just fired. The protein initially glows green. But the fluorescence can permanently switch to red if the protein binds Ca2+ and is hit with violet light. The combination of the two events creates an irreversible structural change that modifies the protein’s fluorescence. This allows the team to use a flash of light to instantly label active neurons in an animal’s brain at a specific moment during an experiment. Then the researchers can look at the brain under a microscope and measure the levels of green and red fluorescence to map out areas of low and high activity. By incorporating the protein’s gene into the brains of fruit flies, the researchers could pinpoint cellular circuits that turn on when the insects encounter certain odor molecules.