Our ability to develop, learn, and adapt depends on the brain’s capacity to change over time. To analyze plasticity processes over time in individual animals, we introduced a novel technique that enables immediate-early gene (IEG) activity to be mapped noninvasively using magnetic resonance imaging (MRI). Using this method, called IEG BLUsH, we interrogated the spatiotemporal relationships between neural activity and plasticity gene induction in an opioid administration paradigm. IEG activity and functional MRI (fMRI) signals were recorded following fentanyl treatments lasting several days (Figure 1). Results revealed overall correspondence of plasticity and activity signatures, but with marked dissociations in brain regions including prefrontal and insular cortex, where IEG induction was particularly strong. Over a week of fentanyl exposure, expression of the IEG reporter increased further in prefrontal cortex, reflecting ongoing engagement of plasticity mechanisms during this period. Interestingly, latency of IEG turn-on decreased over days in some brain regions, suggesting that repeated drug exposure primes the brain for activation of plasticity-related genetic programs. These results show how drug stimuli reshape the brain over time scales from seconds to days, and indicate how IEG BLUsH can help characterize complex patterns of genetic regulation underlying neuroplasticity and other processes in the brain.In response to fentanyl increased BLUsH signal (A), e.g., in striatum (B). Simultaneous fMRI response to (A) showing similar regional pattern (C). (D) Comparison of IEG-BLUsH and fMRI-activity (n=4) highlighting BLUsH-to-fMRI-ratio increase in PFC (arrowhead). (E) Significant change of time-to-peak measurement between day 1 and 7.