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Mol Psychiatry. 2017 Nov;22(11):1512-1519. doi: 10.1038/mp.2017.178. Epub 2017 Sep 12.

Molecular basis of dendritic atrophy and activity in stress susceptibility.

Author information

1
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
2
Division of Renal Diseases and Hypertension, The George Washington University, Washington, DC, USA.
3
Department of Physiology, University of Maryland, University of Maryland, Baltimore, MD, USA.

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.

PMID:
28894298
PMCID:
PMC5747312
DOI:
10.1038/mp.2017.178
[Indexed for MEDLINE]
Free PMC Article

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