BAZ1B in Nucleus Accumbens Regulates Reward-Related Behaviors in Response to Distinct Emotional Stimuli

Abstract

ATP-dependent chromatin remodeling proteins are being implicated increasingly in the regulation of complex behaviors, including models of several psychiatric disorders. Here, we demonstrate that Baz1b, an accessory subunit of the ISWI family of chromatin remodeling complexes, is upregulated in the nucleus accumbens (NAc), a key brain reward region, in both chronic cocaine-treated mice and mice that are resilient to chronic social defeat stress. In contrast, no regulation is seen in mice that are susceptible to this chronic stress. Viral-mediated overexpression of Baz1b, along with its associated subunit Smarca5, in mouse NAc is sufficient to potentiate both rewarding responses to cocaine, including cocaine self-administration, and resilience to chronic social defeat stress. However, despite these similar, proreward behavioral effects, genome-wide mapping of BAZ1B in NAc revealed mostly distinct subsets of genes regulated by these chromatin remodeling proteins after chronic exposure to either cocaine or social stress. Together, these findings suggest important roles for BAZ1B and its associated chromatin remodeling complexes in NAc in the regulation of reward behaviors to distinct emotional stimuli and highlight the stimulus-specific nature of the actions of these regulatory proteins.

BRG1 in the Nucleus Accumbens Regulates Cocaine-Seeking Behavior

“…For example, chronic cocaine exposure results in increased expression of the bromodomain and extraterminal protein BRD4, an epigenetic reader protein (41), and PSMC5, an ATPase-containing subunit of the 19s proteasomal complex (42). We recently demonstrated that an accessory ATPase subunit of the ISWI family of chromatin remodeling complexes, bromodomain adjacent to zinc finger domain 1B, is also upregulated in the NAc (22). …”

“…Self-administration procedures were conducted as previously described (11, 21, 22). Following the 7 d recovery from jugular catheter surgery, rats were assigned to self-administer either saline or 1.0 mg/kg/inf cocaine.…”

Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine

“…Total RNA was isolated from the NAc of individual mice and qRT-PCR was performed as described previously (Sun et al, 2015, Sun et al, 2016). Briefly, bilateral 14 gauge punches of NAc were obtained at varying times after the last cocaine or saline injection and frozen on dry ice until further use.…”

“…ATP–dependent chromatin remodelers also play an important role in regulating gene expression by altering nucleosome positioning, and have been implicated in modulating learning and memory behaviors as well as regulating reward-related behaviors in animal models of depression and drug addiction (Whitehouse et al, 2007, Clapier and Cairns, 2009, Yen et al, 2012, Narlikar et al, 2013, Vogel-Ciernia et al, 2013, Sun et al, 2015, Sun et al, 2016). Specifically, the persistent induction of BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling proteins, has been shown to be important in mediating repeated stress-induced depressive-like behaviors through nucleosome repositioning in NAc (Sun et al, 2015).…”

Chromatin Remodeling in Addiction: BRG1-SMAD3 Interaction Contributes to Cued Reinstatement of Cocaine Seeking

“…To my knowledge, only one other study has examined CRCs in cocaine-related behaviors. Sun et al found that overexpression of Baz1b, an accessory subunit of the imitation switch family of CRCs, drives potentiation of cocaine reward during self-administration in mice, and also confers resilience to chronic social defeat stress (8). …”