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Abstract

The brain's astounding achievements regarding movement control and sensory processing are based on complex spatiotemporal activity patterns in the relevant neuronal networks. Our understanding of neuronal network activity is, however, still poor, not least because of the experimental difficulties to directly observe neural circuits at work in the living brain (in vivo). Over the last decade, new opportunities have emerged especially utilizing 2-photon microscopy to investigate neuronal networks in action. Central to this progress was the development of fluorescent proteins that change their emission depending on cell activity, enabling the visualization of dynamic activity patterns in local neuronal populations. Currently, genetically encoded calcium indicators, proteins which indicate neuronal activity based on action potential-evoked calcium influx, are becoming increasingly used. Long-term expression of these indicators allows repeated monitoring of the same neurons over weeks and months, such that stability and plasticity of their functional properties can be characterized. Furthermore, permanent indicator expression facilitates the correlation of cellular activity patterns and behavior in awake animals. Using examples from recent studies of information processing in mouse neocortex, we review in this article these fascinating new possibilities and discuss the great potential of fluorescent proteins to elucidate the mysteries of neural circuits.