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Molecular basis of dendritic atrophy and activity in stress susceptibility

Molecular Psychiatry volume 22, pages 1512–1519 (2017)Cite this article

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Abstract

Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity. Overall, we identify NAc neuronal-subtype molecular control of dendritic morphology and related functional adaptations, which underlie susceptibility to stress.

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Acknowledgements

We thank Brian N. Mathur and Scott M. Thompson (UMSOM) for input on electrophysiology experiments. This work was supported by NIMH R01MH106500, NIDA R01DA038613 and The One Mind / Janssen Rising Star Translational Research Award.

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Author notes

  1. T C Francis

    Present address: 4Current address: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.,

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Maryland School of Medicine,

    T C Francis, R Chandra, A Gaynor, B Evans, M Engeln & M K Lobo

  2. University of Maryland, Baltimore, MD, USA

    T C Francis, R Chandra, A Gaynor, B Evans, M Engeln & M K Lobo

  3. Division of Renal Diseases and Hypertension, The George Washington University, Washington, DC, USA

    P Konkalmatt

  4. Department of Physiology, University of Maryland, University of Maryland, Baltimore, MD, USA,

    S R Metzbower & T A Blanpied

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Correspondence to M K Lobo.

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Francis, T., Chandra, R., Gaynor, A. et al. Molecular basis of dendritic atrophy and activity in stress susceptibility. Mol Psychiatry 22, 1512–1519 (2017). https://doi.org/10.1038/mp.2017.178

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