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