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Abstract

Measurement of population activity with single-neuron resolution is pivotal for understanding how information is represented and processed in the brain and how the brain's responses are altered by experience. Because neuronal activity in the neocortex is sparse and different neuron types perform different tasks, such measurements need to resolve single action potentials in single neurons, and need to be targeted to neuronal sub-classes. This is greatly facilitated by the use of genetically-encoded fluorescent calcium indicator proteins (FCIPs) of neuronal activity. We have employed recombinant adeno-associated viruses to deliver different FCIPs to neurons at a sufficiently high levels to detect the Ca2+ transients that accompany single action potentials. Based on these transients we were able to detect action potentials with high reliability not only in cultured brain slices but also in cortical layer 2/3 pyramidal cells in living animals. Cell-type targeting and long-term recording thus make FCIPs highly suitable to follow the activity of identified cells over the periods of weeks to months. This allows the study of the development and plasticity of neural maps. Preliminary results suggest that with FCIPs functional imaging of the same cells is possible over periods of