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EJ", "Kukalev A", "Pfisterer UG", "Irastorza-Azcarate I", "Chiariello AM", "Demharter S", "Zea-Redondo L", "Lopez-Atalaya JP", "Nicodemi M", "Akalin A", "Khodosevich K", "Ungless MA", "Winick-Ng W", "Pombo A"], "short_attribution": "Szabo D et al. (2024)", "status": "current", "uuid": "53947f85-e28f-405f-b92e-92ca7bdb2aea", "@type": ["Publication", "Item"], "ID": "PMID:38766140", "display_title": "Szabo D et al. (2024) PMID:38766140", "abstract": "Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs  and play key roles in chronic drug usage (1-3) . As the synaptic and  transcriptional changes that follow an acute cocaine exposure are mostly resolved  within a few days (4,5) , the molecular changes that encode the long-term  cellular memory of the exposure within DNs remain unknown. To investigate whether  a single cocaine exposure induces long-term changes in the 3D genome structure of  DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic  analyses in the mouse midbrain. We found extensive rewiring of 3D genome  architecture at 24 hours past exposure which remains or worsens by 14 days,  outlasting transcriptional responses. The cocaine-induced chromatin rewiring  occurs at all genomic scales and affects genes with major roles in  cocaine-induced synaptic changes. A single cocaine exposure triggers extensive  long-lasting changes in chromatin condensation in post-synaptic and  post-transcriptional regulatory genes, for example the unfolding of Rbfox1 which  becomes most prominent 14 days post exposure. Finally, structurally remodeled  genes are most expressed in a specific DN sub-type characterized by low  expression of the dopamine auto-receptor Drd2 , a key feature of highly  cocaine-sensitive cells. These results reveal an important role for long-lasting  3D genome remodelling in the cellular memory of a single cocaine exposure,  providing new hypotheses for understanding the inception of drug addiction and 3D  genome plasticity.", "title": "A single dose of cocaine rewires the 3D genome structure of midbrain dopamine  neurons.", "journal": "bioRxiv : the preprint server for biology", "@id": "/publications/53947f85-e28f-405f-b92e-92ca7bdb2aea/", "date_published": "2024-05-12", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"abstract": "Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs  and play key roles in chronic drug usage (1-3) . As the synaptic and  transcriptional changes that follow an acute cocaine exposure are mostly resolved  within a few days (4,5) , the molecular changes that encode the long-term  cellular memory of the exposure within DNs remain unknown. To investigate whether  a single cocaine exposure induces long-term changes in the 3D genome structure of  DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic  analyses in the mouse midbrain. We found extensive rewiring of 3D genome  architecture at 24 hours past exposure which remains or worsens by 14 days,  outlasting transcriptional responses. The cocaine-induced chromatin rewiring  occurs at all genomic scales and affects genes with major roles in  cocaine-induced synaptic changes. A single cocaine exposure triggers extensive  long-lasting changes in chromatin condensation in post-synaptic and  post-transcriptional regulatory genes, for example the unfolding of Rbfox1 which  becomes most prominent 14 days post exposure. Finally, structurally remodeled  genes are most expressed in a specific DN sub-type characterized by low  expression of the dopamine auto-receptor Drd2 , a key feature of highly  cocaine-sensitive cells. These results reveal an important role for long-lasting  3D genome remodelling in the cellular memory of a single cocaine exposure,  providing new hypotheses for understanding the inception of drug addiction and 3D  genome plasticity.", "@type": ["Publication", "Item"], "ID": "PMID:38766140", "authors": ["Szabo D", "Franke V", "Bianco S", "Batiuk MY", "Paul EJ", "Kukalev A", "Pfisterer UG", "Irastorza-Azcarate I", "Chiariello AM", "Demharter S", "Zea-Redondo L", "Lopez-Atalaya JP", "Nicodemi M", "Akalin A", "Khodosevich K", "Ungless MA", "Winick-Ng W", "Pombo A"], "@id": "/publications/53947f85-e28f-405f-b92e-92ca7bdb2aea/", "short_attribution": "Szabo D et al. (2024)", "display_title": "Szabo D et al. 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