Sensitive red protein calcium indicators for imaging neural activity

Neurons encode information with brief electrical pulses called spikes. Monitoring spikes in large populations of neurons is a powerful method for studying how networks of neurons process information and produce behavior. This activity can be detected using fluorescent protein indicators, or “probes”, which light up when neurons are active. The best existing probes produce green fluorescence. However, red fluorescent probes would allow us to see deeper into the brain, and could also be used with green probes to image the activity and interactions of different neuron types simultaneously. However, existing red fluorescent probes are not as good at detecting neural activity as green probes. By optimizing two existing red fluorescent proteins, Dana et al. have now produced two new red fluorescent probes, each with different advantages. The new protein indicators detect neural activity with high sensitivity and allow researchers to image previously unseen brain activity. Tests showed that the probes work in cultured neurons and allow imaging of the activity of neurons in mice, flies, fish and worms. History has shown that enhancing the techniques used to study biological processes can lead to fundamentally new insights. In the future, Dana et al. would therefore like to make even more sensitive protein indicators that will allow larger networks of neurons deeper in the brain to be imaged.