This research reveals that opposing alcohol-related memories are stored in distinct neuronal groups, called engrams, within the same cell type in the mouse brain. While acquisition-recruited ensembles promote alcohol relapse, extinction-recruited ensembles work to suppress it by inhibiting dopamine neurons. These two groups are anatomically separated within the dorsomedial striatum, with extinction memories specifically concentrated in the striosome compartment. The study identifies that persistent synaptic strengthening between the prefrontal cortex and these striatal cells serves as the physical substrate for alcohol addiction. By using optogenetics to artificially mimic this strengthening, researchers were able to trigger relapse-like behaviors without any actual alcohol consumption. These findings suggest that precision targeting of these specific neuronal circuits could offer new pathways for treating substance use disorders.

References:

• Xie X, Huang Y, Huang Z, et al. Dual Engram Architecture within a Single Striatal Cell Type Distinctly Controls Alcohol Relapse and Extinction[J]. bioRxiv, 2026: 2026.01. 13.699375.