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Ablation of D2 autoreceptors causes epigenetic reprogramming of cortical neurons

Molecular Psychiatry volume 19, page 1153 (2014)Cite this article

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Legend: Cell-specific ablation of dopamine (DA) D2 receptors (D2Rs) from DA neurons (autoreceptors; DA-D2RKO mice) affects the activity of these neurons (J Neurosci 2012; 32: 9023–9034). Comparative analyses performed in areas that receive dopaminergic fibers (PFC and NAcc) in WT and DA-D2RKO mice show the presence of a selective epigenetic reprogramming specific for the PFC of mutant mice. We found a robust increase of repressive histone marks (methylation) on Lysine 9 of histone H3 (H3K9me3) in DA-D2RKO PFCs as compared with WT. Increased H3K9me3 (green) was observed in NeuN-positive cortical neurons (red). These chromatin modifications mirror a potent silencing of gene expression (~2000 genes downregulated) in DA-D2RKO PFCs as compared with WT (heat maps; right). These molecular events are associated with several behavioral deficits, which are classically observed in animal models of schizophrenia (see Table). Altogether, these studies indicate that dysfunctional control of DA levels is able to induce wide genomic and behavioral alterations through epigenetic mechanisms. For more information on this topic, please refer to the article by Brami-Cherrier et al. on pages 1193–1200.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA,

    K Brami-Cherrier, A Anzalone, M Ramos & E Borrelli

  2. INSERM/UCI U904, University of California, Irvine, CA, USA,

    K Brami-Cherrier, A Anzalone, M Ramos & E Borrelli

  3. Center for Epigenetics and Metabolism, University of California, Irvine, CA, USA,

    K Brami-Cherrier, A Anzalone, M Ramos, F Macciardi, A Imhof & E Borrelli

  4. Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilians University of Munich, Munich, Germany

    I Forne & A Imhof

  5. Adolf-Butenandt Institute, Ludwig Maximilians University of Munich, Munich, Germany

    I Forne & A Imhof

  6. Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA,

    F Macciardi

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  1. K Brami-Cherrier
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  2. A Anzalone
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  3. M Ramos
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  4. I Forne
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  6. A Imhof
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  7. E Borrelli
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Brami-Cherrier, K., Anzalone, A., Ramos, M. et al. Ablation of D2 autoreceptors causes epigenetic reprogramming of cortical neurons. Mol Psychiatry 19, 1153 (2014). https://doi.org/10.1038/mp.2014.144

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