To establish brain-wide surveys of the areas and neural circuits involved in sensorimotor learning, we have begun to investigate mice designed for targeted recombination in active populations (Fos[2A-iCreER], TRAP2 mice) enabling activity-dependent expression of a Cre-dependent fluorescent reporter within a specific time window. As a first test, we exposed TRAP2 mice to a novel enriched environment after trimming of all whiskers but one and observed a significant increase in the number of TRAPed cells in the barrel cortex compared to control mice. Moreover, minimal expression of the fluorescent reporter occurred in mice not intraperitoneally injected with tamoxifen, indicating that the TRAP2 system has very little leak. We aim to label cells undergoing plasticity across the whole brain while mice learn a rapid single-session whisker-based perceptual decision-making task. To obtain the location and morphologies of the cells, we use whole-brain organic solvent based clearing protocols, such as iDISCO. An essential step in iDISCO involves the immunostaining of the fluorescent reporter expressed by activation of the TRAP2 system, which we found could be carried out using primary antibodies directly-conjugated to a fluorophore, eliminating the need for secondary amplification, which can cause artefacts. Light-sheet imaging of transparent immunostained samples aligned to a digital brain atlas allows quantification of brain areas with differential numbers of TRAPed cells across various experimental conditions. We think this experimental paradigm might help provide an important foundation for studying the areas and neural circuits involved in sensorimotor learning across the mouse brain.