Abstract
Stress alters the structure and function of brain reward circuitry and is an important risk factor for developing depression. In the nucleus accumbens (NAc), structural and physiological plasticity of medium spiny neurons (MSNs) have been linked to increased stress-related and depression-like behaviors. NAc MSNs have opposing roles in driving stress-related behaviors that is dependent on their dopamine receptor expression. After chronic social defeat stress, NAc MSNs exhibit increased dendritic spine density. However, it remains unclear if the dendritic spine plasticity is MSN subtype specific. Here we use viral labeling to characterize dendritic spine morphology specifically in dopamine D2 receptor expressing MSNs (D2-MSNs). After chronic social defeat, D2-MSNs exhibit increased spine density that is correlated with enhanced social avoidance behavior. Together, our data indicate dendritic spine plasticity is MSN subtype specific, improving our understanding of structural plasticity after chronic stress.
Highlights
Stress alters the structure and function of brain reward circuitry and is an important risk factor for developing depression
To test the hypothesis that spine density is altered in D2-medium spiny neurons (MSNs), we infused a low titer Cre dependent eYFP or mCherry to sparsely label D2 receptor expressing MSNs (D2-MSNs) in the NAc8
This work establishes that dendritic spine density occurring after chronic social defeat stress is driven by changes to D2-MSNs
Summary
Stress alters the structure and function of brain reward circuitry and is an important risk factor for developing depression. In the nucleus accumbens (NAc), structural and physiological plasticity of medium spiny neurons (MSNs) have been linked to increased stress-related and depression-like behaviors. After chronic social defeat stress, NAc MSNs exhibit increased dendritic spine density. It remains unclear if the dendritic spine plasticity is MSN subtype specific. A vast preclinical and human functional imaging literature implicates disrupted brain reward circuitry in the symptomology of d epression[5,6] These changes are a consequence of cellular, molecular, and structural adaptations that lead to altered neuronal activity. Excitatory input is only increased onto D2-MSNs, and is instead weakened onto D1-MSNs20 Given these opposing physiological changes in MSN subtypes, and an apparent lack of spine changes on D1-MSNs9, we hypothesized D2-MSNs have increased dendritic spine density after CSDS. We used viral labeling of D2-MSNs with the D2-MSN specific A2A-Cre line to characterize dendritic spines in mice subjected to CSDS and find density of specific D2-MSNs dendritic spine types correlates with social avoidance behavior
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