MDMA enhances prefrontal plasticity and representational drift during fear extinction
bioRxiv (Cold Spring Harbor Laboratory) March 8, 2026 Nitzan Geva, Sarah J. Jefferson, Emi Krishnamurthy et al.
MDMA increases spine density and the formation of new spines in the medial prefrontal cortex of mice, as shown by two-photon microscopy. Calcium imaging in the infralimbic cortex during fear extinction revealed that neural activity in this region became more correlated with the suppression of freezing behavior, indicating a strengthened role in extinction. Longitudinal cell registration showed accelerated representational drift across days in MDMA-treated mice, especially in neurons that suppressed activity to conditioned cues. These findings indicate that MDMA facilitates structural and functional neuroplasticity, which may underlie its enhancement of extinction learning.