Extended supplementary data for manuscript: A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons

Cocaine, and other addictive drugs, can induce long-term synaptic modifications in midbrain dopamine neurons (DNs) which play key roles in the development of addiction, but the cellular basis of these long-term changes are not well understood. In this work, we applied Genome Architecture Mapping and single nucleus transcriptomic analyses in mouse midbrain DNs and found extensive rewiring of 3D genome architecture lasting 1 and 14 days upon a single cocaine exposure. The affected genes have major roles in cocaine responses and are preferentially expressed in a DN sub-type that projects to secondary reward-pathway regions. These results reveal an unexpected role for 3D genome remodelling in the long-term memory of a single cocaine exposure, providing new insights about the inception of drug addiction and 3D genome plasticity.