Molecular basis of dendritic atrophy and activity in stress susceptibility
Mol Psychiatry. 2017-09-12; 22(11): 1512-1519
DOI: 10.1038/mp.2017.178
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Francis TC(1), Chandra R(1), Gaynor A(1), Konkalmatt P(2), Metzbower SR(3), Evans B(1), Engeln M(1), Blanpied TA(3), Lobo MK(1).
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.
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.