Molecular basis of dendritic atrophy and activity in stress susceptibility

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy / genetics
  • Atrophy / metabolism
  • Dendrites / genetics
  • Dendrites / metabolism
  • Dendrites / physiology
  • Depression / physiopathology
  • Depressive Disorder / physiopathology
  • Disease Susceptibility
  • Early Growth Response Protein 3 / genetics
  • Early Growth Response Protein 3 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / genetics
  • Neurons / physiology
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology*
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Stress, Psychological / physiopathology*

Substances

  • Egr3 protein, mouse
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Early Growth Response Protein 3