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.

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

“…However our data are difficult to interpret given the competing effects of fentanyl and stress. Additionally, RhoA expression and dendritic remodeling after CSDS are cell subtype specific (Fox et al, 2020b(Fox et al, , 2020a, and there is no work on NAc GTPases after CWDS. Future work can dissect precise cell-type specific adaptations that may explain the effects of CSDS/CWDS on subsequent fentanyl consumption.…”

“…Both chronic stress and opioid exposure cause structural changes in the nucleus accumbens (NAc) that are thought to drive stress-susceptibility or increased drug intake (Matsubara et al, 1999;Robinson et al, 2002;Spiga et al, 2005;Diana et al, 2006;Christoffel et al, 2011bChristoffel et al, , 2011aPal and Das, 2013;Golden et al, 2013;Guegan et al, 2016;Kobrin et al, 2016;Graziane et al, 2016;Francis et al, 2017;Cahill et al, 2018;Geoffroy et al, 2019;Fox et al, 2020aFox et al, , 2020b. We thus examined the consequences of our combined stress and fentanyl paradigm on genes associated with dendritic remodeling (Nakayama et al, 2000;Negishi and Katoh, 2005;Newey et al, 2005;Chen and Firestein, 2007).…”

“…Social stress was performed as in our previous work (Fox et al, 2020a(Fox et al, , 2020bEngeln et al, 2021;Morais-Silva et al, 2021), by using the modifications described in (Warren et al, 2013;Iñiguez et al, 2018) for vicarious resident-intruder stress. In chronic social defeat stress (CSDS), a male mouse (intruder) is physically defeated by an aggressive CD-1 (resident) for 10 min in a hamster cage containing woodchip bedding and a perforated divider.…”

“…Like (Cooper et al, 2017), we used the standardized chronic social defeat stress (CSDS) procedure. (Berton et al, 2006;Krishnan et al, 2007;Golden et al, 2011;Fox et al, 2020bFox et al, , 2020a. CSDS produces anhedonia in the majority of mice (~60%, termed "stress-susceptible"), along with a decrease in motivated behaviors such as social interaction (Krishnan et al, 2007;Der-Avakian et al, 2014;Heshmati and Russo, 2015;Fox and Lobo, 2019).…”

Effects of gonadectomy and dihydrotestosterone on neuronal plasticity in motivation and reward related brain regions in the male rat

“…For each brain region, two or three dendritic segments (70‐200 µm away from soma, and more than 10 µm away from dendritic end points and bifurcations) per neurone (completely and brightly labelled, isolated from other labelled neurones), in two to six neurones (three neurones for the far majority of data points), were imaged and analysed (Figure 1). Our assessment and statistical analyses of dendritic spine densities is based upon a rigorous approach that we and others have previously used 8,19,34,36‐38 . With nine or ten animals/group, this equates to approximately 80‐90 dendritic segments (and thousands of spines) per group per brain region.…”