Dendritic spine density is increased on nucleus accumbens D2 neurons after chronic social defeat

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.

Figure 1

(a) Experimental timeline. A2A-Cre mice were injected with AAV-eYFP or AAV-mCherry to label D2-MSNs prior to chronic social defeat stress (CSDS). (b) Social interaction behavior after 10 days CSDS or in unstressed controls. Data points represent individual mice. (c) Representative image of sparsely labeled MSNs in the NAc and schematic for dendritic spine analysis workflow. Secondary dendrites of single D2-MSNs are imaged at 63x, then analyzed in Neuron Studio. Identified spines are confirmed in 3D reconstructed segments.

Figure 2

(a) Spine density in unstressed control and socially defeated mice, and broken down by spine type. Each individual data point represents the average of 3–4 dendrites per cell, from 3–4 cells in an individual mouse (9–15 total dendrites per mouse) (b) Representative dendritic segments from control and CSDS mice. *P < 0.05, **P < 0.01, ***P < 0.005, Welch’s corrected T-test.

Figure 3

Correlations between social interaction behavior and spine density in control (white circles) and CSDS mice (black circles), and broken down by spine type. Black lines and inset R and P-values are the linear regression of both CSDS and control mice together. Gray lines are the regression of CSDS mice alone. SI Ratio is time spent in the interaction zone of a social interaction test with a novel target present divided by the time when novel target is absent.