Technologies for large-scale mapping of functional neural circuits active during a user-defined time window.

The mapping of neural circuits activated during behavior down to individual neurons is crucial for decoding how the brain processes information. Technologies allowing activity-dependent labeling of neurons during user-defined restricted time windows are rapidly developing. Precise marking of the time window with light, in addition to chemicals, is now possible. In these technologies, genetically encoded molecules integrate molecular events resulting from neuronal activity with light/drug-dependent events. The outputs are either changes in fluorescence or activation of gene expression. Molecular reporters allow labeling of activated neurons for visualization and cell-type identification. The transcriptional readout also allows further control of activated neuronal populations using optogenetic tools as reporters. Here we review the design of these technologies and discuss their demonstrated applications to reveal previously unknown connections in the mammalian brain. We also consider the strengths and weaknesses of the current approaches and provide a perspective for the future.