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Extended supplementary data for manuscript: Gene regulatory mechanisms of cellular memory of a single cocaine exposure in VTA dopaminergic neurons

Item Type:Dataset
Title:Extended supplementary data for manuscript: Gene regulatory mechanisms of cellular memory of a single cocaine exposure in VTA dopaminergic neurons
Creators: Zea-Redondo, Luna ORCID logoORCID: https://orcid.org/0000-0001-9064-9126, Franke, Vedran ORCID logoORCID: https://orcid.org/0000-0003-3606-6792, Paul, Eleanor J., Kukalev, Alexander ORCID logoORCID: https://orcid.org/0000-0001-5847-3773, Arguedas Jimenez, Laura ORCID logoORCID: https://orcid.org/0009-0004-2240-7781, Braeuning, Caroline ORCID logoORCID: https://orcid.org/0009-0007-1439-9920, Marin, Oscar, Akalin, Altuna ORCID logoORCID: https://orcid.org/0000-0002-0468-0117, Ungless, Mark A., Winick-Ng, Warren ORCID logoORCID: https://orcid.org/0000-0002-8716-5558 and Pombo, Ana ORCID logoORCID: https://orcid.org/0000-0002-7493-6288
Abstract:Drug addiction is a chronic brain disease with major global health and economic costs. Many drugs of abuse hijack reward circuitry, reinforcing drug-taking behaviour. While drug effects on synaptic plasticity are transient, the gene regulatory mechanisms driving long-term memory of drug exposure remain unclear. We assessed gene expression and chromatin accessibility in ventral tegmental area dopamine neurons (VTA-DNs) in a time-course following acute cocaine exposure. Expression changes persist for 14 days, including upregulation of addiction-associated neuropeptides, while AP-1 chromatin binding sites shift from early stimulus-driven activity to sustained silencing. We show downregulation of Foxa2 and its targets, followed by erosion of DN identity lasting up to 14 days, and sustained upregulation of Polycomb-repressed genes. We show that a single cocaine exposure is sufficient to trigger enduring transcriptional and epigenetic changes in reward-associated neurons as memory of drug exposure, and provide a high-resolution temporal map of cocaine-induced regulatory plasticity as groundwork for finding molecular targets that drive addiction onset.
Source:Zenodo
Publisher:CERN
Date:4 September 2025
Official Publication:https://doi.org/10.5281/zenodo.16994739

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